Page last updated: 2024-11-12

natriuretic peptide, c-type

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Natriuretic Peptide, C-Type: A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID16179407
MeSH IDM0029831

Synonyms (19)

Synonym
natriuretic peptide, c-type
atriopeptin c (pig)
127869-51-6
c-type natriuretic peptide
unii-3vcd78874l
3vcd78874l ,
cnp-22
c-type natriuretic peptide (1-22) (human, rat, swine)
AKOS024457659
natriuretic peptide, c-type, >=95% (hplc)
c-type natriuretic peptide (32-53) (human, porcine, rat)
natriuretic peptide, c-type, human and porcine - cas 127869-51-6
bdbm287915
cnp-53
us10087144, compound cnp
c-type natriuretic peptide (cnp) (1-22), humanc-type natriuretic peptide (cnp) (1-22), human
cnp (1-22), human
DTXSID60155686
natriuretic peptide,c-type

Research Excerpts

Toxicity

ExcerptReferenceRelevance
"The objective of the study was to compare serial changes in maternal plasma CNP peptides during normal pregnancy with changes in pregnancy complicated by adverse events and relate these to fetal growth and placental CNP content."( C-type natriuretic peptide in complicated pregnancy: increased secretion precedes adverse events.
Darlow, BA; Espiner, EA; Gullam, JE; Prickett, TC; Pullar, BE; Reid, RA, 2014
)
0.4
"We studied changes in maternal plasma aminoterminal proCNP (NTproCNP) and CNP at monthly intervals, fetal growth, and placental and umbilical plasma CNP peptides in 51 women, 28 of whom experienced an adverse event and 23 were uneventful."( C-type natriuretic peptide in complicated pregnancy: increased secretion precedes adverse events.
Darlow, BA; Espiner, EA; Gullam, JE; Prickett, TC; Pullar, BE; Reid, RA, 2014
)
0.4
"Maternal NTproCNP is significantly raised in women who later exhibit a range of obstetric adverse events."( C-type natriuretic peptide in complicated pregnancy: increased secretion precedes adverse events.
Darlow, BA; Espiner, EA; Gullam, JE; Prickett, TC; Pullar, BE; Reid, RA, 2014
)
0.4
" The toxic changes related to bone and cartilage tissues were not observed in any animal with a closed epiphyseal plate, indicating that the toxic changes were triggered by the growth-accelerating effect on the bone and cartilage."( Safety assessment of a novel C-type natriuretic peptide derivative and the mechanism of bone- and cartilage-specific toxicity.
Abe, Y; Furuya, M; Jindo, T; Kangawa, K; Maeda, H; Minamitake, Y; Morozumi, N; Nakamura, R; Nishimura, T; Ogasawara, H; Yotsumoto, T, 2019
)
0.51
" No new adverse effects of vosoritide were detected."( Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.
Alanay, Y; Arundel, P; Bacino, CA; Basel, D; Bober, MB; Charrow, J; Day, JRS; Fisheleva, E; Font, RU; Ginebreda, I; Harmatz, P; Hoernschemeyer, D; Hoover-Fong, J; Huntsman-Labed, A; Irving, M; Jayaram, K; Kotani, Y; Leiva-Gea, A; Luna-González, F; Mochizuki, H; Mohnike, K; Ozono, K; Polgreen, LE; Porco, DM; Rutsch, F; Saal, HM; Savarirayan, R; Tofts, L; White, KK; Wilcox, WR; Yasui, N, 2021
)
0.62
"Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years."( Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.
Alanay, Y; Arundel, P; Bacino, CA; Basel, D; Bober, MB; Charrow, J; Day, JRS; Fisheleva, E; Font, RU; Ginebreda, I; Harmatz, P; Hoernschemeyer, D; Hoover-Fong, J; Huntsman-Labed, A; Irving, M; Jayaram, K; Kotani, Y; Leiva-Gea, A; Luna-González, F; Mochizuki, H; Mohnike, K; Ozono, K; Polgreen, LE; Porco, DM; Rutsch, F; Saal, HM; Savarirayan, R; Tofts, L; White, KK; Wilcox, WR; Yasui, N, 2021
)
0.62
" The primary endpoint was frequency of adverse events and other safety outcomes."( Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP.
Breinholt, VM; Christoffersen, ED; Mygind, PH; Ota, S; Viuff, D; Will Charlton, R; Zhang, Y, 2022
)
0.72
" TransCon CNP was well-tolerated, with no serious treatment-emergent adverse events or discontinuations."( Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP.
Breinholt, VM; Christoffersen, ED; Mygind, PH; Ota, S; Viuff, D; Will Charlton, R; Zhang, Y, 2022
)
0.72

Pharmacokinetics

ExcerptReferenceRelevance
" The plasma half-life of CNP on termination of infusion was rapid (1."( Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep.
Charles, CJ; Espiner, EA; Nicholls, MG; Richards, AM; Yandle, TG, 1995
)
0.29
" Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose-tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration."( Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats.
Bothwell, JC; Espiner, EA; Prickett, TC; Richards, AM; Yandle, TG, 2012
)
0.38

Compound-Compound Interactions

ExcerptReferenceRelevance
" These results suggested that CNP in combination with sildenafil exerts antiproliferative effects on RMS cells by inhibiting the Raf/MEK/ERK pathway."( C-type natriuretic peptide in combination with sildenafil attenuates proliferation of rhabdomyosarcoma cells.
Hosoda, H; Kangawa, K; Kimura, T; Miura, K; Miyazato, M; Nakahata, K; Nojiri, T; Okuyama, H; Uehara, S; Zenitani, M, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
" sCNP was a potent stimulator of chloride secretion similar in its dose-response curve to vasoactive intestinal peptide."( C-type natriuretic peptides stimulate chloride secretion in the rectal gland of Squalus acanthias.
McEnroe, G; Porter, JG; Protter, A; Silva, P; Solomon, R, 1992
)
0.28
" This inhibition reflects the ability of GnRH to shift the CNP dose-response curve rightward (increasing the EC50 for CNP action approximately 10-fold both with and without 3-isobutyl-1-methylxanthine)."( Cyclic guanosine monophosphate production in the pituitary: stimulation by C-type natriuretic peptide and inhibition by gonadotropin-releasing hormone in alpha T3-1 cells.
Käppler, K; McArdle, CA; Poch, A, 1993
)
0.29
" Cyclic GMP dose-response curves to CNP failed to show any signs of saturation even at concentrations up to 30 microM, indicating a relatively low affinity of CNP for the GC-B receptor."( Characterization of natriuretic peptide receptor subtypes in the AtT-20 pituitary tumour cell line.
Cramb, G; Gilkes, AF; Guild, SB; Ogden, PH, 1994
)
0.29
" Dose-response studies revealed that the inhibitory effects of CNP and ANF on PAI-1 expression were concentration dependent, with IC50s of approximately 1 nmol/L for both natriuretic peptides."( Natriuretic factors and nitric oxide suppress plasminogen activator inhibitor-1 expression in vascular smooth muscle cells. Role of cGMP in the regulation of the plasminogen system.
Bouchie, JL; Feener, EP; Hansen, H, 1998
)
0.3
" Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease."( Five cardiac hormones decrease the number of human small-cell lung cancer cells.
Alli, AA; Fitz, SR; Gower, WR; Sanchez-Ramos, J; Solivan, SM; Song, S; Vesely, BA; Vesely, DL, 2005
)
0.33
" Biochemical dosage was applied to study the possible mechanisms that may cause the proposita's phenotype."( Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation.
Bader, M; Beri, S; Bocciardi, R; Buttgereit, J; Divizia, MT; Garofalo, S; Gimelli, G; Gimelli, S; Giorda, R; Lerone, M; Ravazzolo, R; Tavella, S; Zuffardi, O, 2007
)
0.34
" Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed."( Insights into natriuretic peptides in heart failure: an update.
Boerrigter, G; Burnett, JC; Korinek, J; Mohammed, SF, 2008
)
0.35
"01) in dose-response studies enhanced human osteoblasts' proliferation."( Vessel dilator and C-type natriuretic peptide enhance the proliferation of human osteoblasts.
Bennett, M; Lenz, A; Skelton, WP; Vesely, DL, 2010
)
0.36
" BNP and NT-proBNP were dosed with commercial kits."( Depletion of proBNP1-108 in patients with heart failure prevents cross-reactivity with natriuretic peptides.
Cristol, JP; Davy, JM; Delseny, D; Dupuy, AM; Fareh, J; Guerrier, L; Larue, C; Leclercq, F; Merle, D; Pasquie, JL; Roubille, F; Salvetat, N, 2013
)
0.39
" Thus, pharmaceutical formulation approaches for sustained-release dosage forms to allow chronic exposure to ASB20123 might be suitable to ensure drug effectiveness and safety."( ASB20123: A novel C-type natriuretic peptide derivative for treatment of growth failure and dwarfism.
Furuya, M; Jindo, T; Kangawa, K; Maeda, H; Minamitake, Y; Morozumi, N; Nakamura, R; Yamaki, A; Yoshida, S; Yoshikiyo, K; Yotsumoto, T, 2019
)
0.51
"Safety and PD data from this phase 1 trial support that TransCon CNP is well tolerated, with a PK profile compatible with a once-weekly dosing regimen."( Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP.
Breinholt, VM; Christoffersen, ED; Mygind, PH; Ota, S; Viuff, D; Will Charlton, R; Zhang, Y, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,387)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's409 (29.49)18.2507
2000's452 (32.59)29.6817
2010's424 (30.57)24.3611
2020's102 (7.35)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 46.27

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index46.27 (24.57)
Research Supply Index7.28 (2.92)
Research Growth Index4.54 (4.65)
Search Engine Demand Index73.08 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (46.27)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials31 (2.19%)5.53%
Reviews179 (12.67%)6.00%
Case Studies5 (0.35%)4.05%
Observational7 (0.50%)0.25%
Other1,191 (84.29%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (9)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Serum Levels of C Type Natriuretic Peptide in Reproductive Age, Perimenopausal and Postmenopausal Women [NCT04000815]71 participants (Actual)Interventional2019-07-24Completed
The Effects of C-type Natriuretic Peptide on Endothelial Function Following Ischaemia-Reperfusion in the Human Forearm [NCT01075776]0 participants (Actual)Interventional2020-01-31Withdrawn(stopped due to Lack of funding)
C Type Natriuretic Peptide and Polycystic Ovary Syndrome [NCT04006171]90 participants (Actual)Interventional2019-07-15Completed
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia [NCT03197766]Phase 3121 participants (Actual)Interventional2016-12-12Completed
A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia [NCT02724228]Phase 230 participants (Actual)Interventional2016-01-26Active, not recruiting
A Phase 1, Randomized, Open-Label, Sponsor-Open, Two-Sequence, Two-Period Crossover Study to Investigate the Bioequivalence of a Single Subcutaneous Dose of BMN 111 Administered Using Either a Vial and Syringe or Injector Pen in Healthy Adult Participants [NCT05813314]Phase 136 participants (Actual)Interventional2023-03-15Terminated(stopped due to The BMN 111-104 study has terminated as further optimization of the approach to achieve bio equivalence is required. The study termination was not due to any patient safety concerns.)
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months [NCT03583697]Phase 275 participants (Actual)Interventional2018-05-23Completed
A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia [NCT03424018]Phase 3119 participants (Actual)Interventional2017-12-12Active, not recruiting
A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia [NCT02055157]Phase 235 participants (Actual)Interventional2014-01-13Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02055157 (23) [back to overview]Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Initial 6-months
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Initial 6-months
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Upper Arm Length to Lower Arm (Forearm) Length Ratio During Initial 6-Months
NCT02055157 (23) [back to overview]Change From Baseline in Height Z-Scores Using Centers for Disease Control and Prevention (CDC) Reference Standard During Initial 6-Months
NCT02055157 (23) [back to overview]Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Arm Span to Height Ratio During Initial 6-months
NCT02055157 (23) [back to overview]Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Annualized Growth Velocity (AGV) During Initial 6-Month
NCT02055157 (23) [back to overview]Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 3 and 4
NCT02055157 (23) [back to overview]Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 1 and 2 Switchers
NCT02055157 (23) [back to overview]Change From Baseline in Upper to Lower Body Ratios During Initial 6-Months
NCT02055157 (23) [back to overview]Overall Summary of Adverse Events During Entire Study Period
NCT02055157 (23) [back to overview]Overall Summary of Adverse Events During Initial 6-Month Period
NCT03197766 (4) [back to overview]Summary of Subjects Experiencing Adverse Events (AEs) During Treatment
NCT03197766 (4) [back to overview]Change From Baseline in Annualized Growth Velocity (AGV) at Week 52
NCT03197766 (4) [back to overview]Change From Baseline in Height Z-score at Week 52
NCT03197766 (4) [back to overview]Change From Baseline in Upper to Lower Segment Body Ratio at Week 52
NCT04000815 (4) [back to overview]Correlation Between Serum CNP and Follicle Stimulating Hormone and Luteinizing Hormone Levels in Groups 1 and 2
NCT04000815 (4) [back to overview]Serum C Type Natriuretic Peptide Levels
NCT04000815 (4) [back to overview]Correlation Between Serum CNP and Estradiol Levels in Groups 1 and 2
NCT04000815 (4) [back to overview]Correlation Between Serum CNP and Antral Follicle Count (AFC) in Groups 1 and 2
NCT04006171 (16) [back to overview]Serum Tiroid Stimulating Hormone of PCOS and Healthy Women
NCT04006171 (16) [back to overview]High Density Lipoprotein and Low Density Lipoprotein Levels of Participants
NCT04006171 (16) [back to overview]Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum Prolactin Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum Insulin Levels of Participants
NCT04006171 (16) [back to overview]Serum Free Testosterone Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum Estradiol Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum Dehydroepiandrosterone Sulfate (DHEAS) Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum CNP Levels of PCOS and Healthy Participants
NCT04006171 (16) [back to overview]Serum Androstenedione Levels of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Roc Curve of CNP
NCT04006171 (16) [back to overview]Free Androgen Index of Participants
NCT04006171 (16) [back to overview]Homeostatic Model Assessment of Insulin Resistance of Participants
NCT04006171 (16) [back to overview]Serum Glucose, Total Cholesterol and Triglycerides Levels of Participants
NCT04006171 (16) [back to overview]Comparison of FSH and LH of PCOS and Healthy Women
NCT04006171 (16) [back to overview]Serum Total Testosterone Levels of PCOS and Healthy Women

Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 3 and 4

The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height) (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to Month 24
Cohort 31.911-0.067
Cohort 41.962-0.121

[back to top]

Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 1 and 2 Switchers

The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height) (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 12.119-0.078
Cohort 22.053-0.078

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 3 and 4

The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to Month 24
Cohort 31.1070.014
Cohort 41.061-0.012

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers

The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 11.080-0.020
Cohort 21.1000.018

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Initial 6-months

The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Leg Length (Thigh) / Knee to Heel Length. (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
Interventionratio (Mean)
BaselineChange from Baseline to Day 183
Cohort 10.672-0.002
Cohort 20.662-0.006
Cohort 30.6870.007
Cohort 40.691-0.006

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Initial 6-months

The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 6 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length. (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
Interventionratio (Mean)
BaselineChange from Baseline to Day 183
Cohort 11.0890.001
Cohort 21.0740.007
Cohort 31.1070.034
Cohort 41.0610.015

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 3 and 4

The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to Month 24
Cohort 30.6870.010
Cohort 40.691-0.033

[back to top]

Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers

The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 10.6590.002
Cohort 20.6730.006

[back to top]

Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 3 and 4

The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to Month 24
Cohort 31.1300.037
Cohort 41.106-0.027

[back to top]

Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers

The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 11.1310.009
Cohort 21.114-0.004

[back to top]

Change From Baseline in Upper Arm Length to Lower Arm (Forearm) Length Ratio During Initial 6-Months

The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length. (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
Interventionratio (Mean)
BaselineChange from Baseline to Day 183
Cohort 11.130-0.019
Cohort 21.1430.001
Cohort 31.130-0.048
Cohort 41.1060.003

[back to top]

Change From Baseline in Height Z-Scores Using Centers for Disease Control and Prevention (CDC) Reference Standard During Initial 6-Months

"Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 Standard Deviation Scores (SDs) indicate a child's height is no longer within normal height range for average stature children of the same sex and age.~Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC)." (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
Interventionz score (Mean)
BaselineChange from Baseline to Day 183
Cohort 1-6.056-0.008
Cohort 2-5.1450.078
Cohort 3-4.6130.229
Cohort 4-5.1930.265

[back to top]

Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 3 and 4

"Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.~Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC)." (NCT02055157)
Timeframe: At month 24

,
Interventionz score (Mean)
BaselineChange from Baseline to Month 24
Cohort 3-4.6130.788
Cohort 4-5.1930.896

[back to top]

Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 1 and 2 Switchers

"Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.~Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC)." (NCT02055157)
Timeframe: At month 24

,
Interventionz score (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 1-6.0640.520
Cohort 2-4.9120.259

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Change From Baseline in Arm Span to Height Ratio During Initial 6-months

The Arm Span to Height Ratio prior to treatment, at baseline, and through 6 months is assessed by Arm Span / Standing Height. (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
Interventionratio (Mean)
BaselineChange from Baseline to Day 183
Cohort 10.9010.012
Cohort 20.889-0.005
Cohort 30.9130.007
Cohort 40.8930.001

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Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 1 and 2 Switchers

"The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height.~Values are not available for participants in cohort 1 switchers for Change from Baseline to >=12 Months on 15ug/kg." (NCT02055157)
Timeframe: At month 24

Interventionratio (Mean)
BaselineChange from Baseline to >=12 Months on 15ug/kg
Cohort 20.881-0.014

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Change From Baseline in Annualized Growth Velocity (AGV) During Initial 6-Month

Annualized Growth Velocity at Day 183 is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25. (NCT02055157)
Timeframe: At 6 month (Day 183)

,,,
Interventioncm/year (Mean)
BaselineChange from Baseline to Day 183
Cohort 13.755-0.371
Cohort 22.8911.276
Cohort 34.0442.014
Cohort 44.4922.085

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Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 3 and 4

Annualized Growth Velocity at Day 183 visit is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25. (NCT02055157)
Timeframe: At month 24

,
Interventioncm/year (Mean)
BaselineChange from Baseline to Month 24
Cohort 34.0441.744
Cohort 44.4921.538

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Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 3 and 4

The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height. (NCT02055157)
Timeframe: At month 24

,
Interventionratio (Mean)
BaselineChange from Baseline to Month 24
Cohort 30.9110.000
Cohort 40.900-0.006

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Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 1 and 2 Switchers

Annualized Growth Velocity at 1st visit with >= 12 months on 15ug/kg is assessed on standing height as ((Height at 1st Visit with >= 12 Months on 15 μg/kg - Height at 1st Visit on 15 μg/kg)/(Date of the 1st Visit with >= 12 months on 15 μg/kg - Date of at 1st Visit on 15 μg/kg)) x 365.25. (NCT02055157)
Timeframe: At month 24

,
Interventioncm/year (Mean)
BaselineChange from Baseline at >=12 Months on 15μg/kg
Cohort 13.6291.846
Cohort 23.5102.245

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Change From Baseline in Upper to Lower Body Ratios During Initial 6-Months

The Upper to Lower Body ratio prior to treatment, at baseline, and through 6 months is assessed on Sitting Height / (Standing Height - Sitting Height) (NCT02055157)
Timeframe: At month 6 (Day 183)

,,,
InterventionRatio (Mean)
BaselineChange from Baseline to Day 183
Cohort 12.094-0.021
Cohort 22.0270.003
Cohort 31.911-0.024
Cohort 41.962-0.030

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Overall Summary of Adverse Events During Entire Study Period

"A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.~TEAE - Treatment-emergent adverse event. SAE - Serious adverse event." (NCT02055157)
Timeframe: Up to Month 25 ± 7 Days

,,,
InterventionParticipants (Count of Participants)
Subjects with at Least 1 Reported TEAESubjects Least Reported Study Drug-Related TEAESubjects with at Least 1 Reported SAESubjects Least Reported Study Drug-Related SAESubjects Who Died
Cohort 187100
Cohort 288000
Cohort 3109100
Cohort 499100

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Overall Summary of Adverse Events During Initial 6-Month Period

"A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.~Serious adverse event (SAE)." (NCT02055157)
Timeframe: Up to Month 6 ± 7 Days

,,,
InterventionParticipants (Count of Participants)
Subjects with at Least 1 Reported TEAESubjects Least Reported Study Drug-Related TEAESubjects with at Least 1 Reported SAESubjects Least Reported Study Drug-Related SAESubjects Who Died
Cohort 187000
Cohort 288000
Cohort 3109000
Cohort 499000

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Summary of Subjects Experiencing Adverse Events (AEs) During Treatment

"AEs with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included.~serious adverse event (SAE)" (NCT03197766)
Timeframe: Up to Week 56

,
Interventionparticipants (Number)
Subjects with any AESubjects with any SAESubjects with any treatment-related AESubjects who died
BMN 111 - 15 μg/kg593530
Placebo604510

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Change From Baseline in Annualized Growth Velocity (AGV) at Week 52

"AGV at a Post-baseline Visit is defined as [(Height at Post-baseline Visit - Height at Baseline)/(Date of Post-baseline Visit - Date of Baseline Assessment)] x 365.25~AGV at Baseline is defined as [(Height at Baseline - last height measurement in Study 111-901 at least 6 months prior to Baseline)/(Date of Baseline Assessment - Date of last height measurement in Study 111-901 at least 6 months prior to Baseline)] x 365.25" (NCT03197766)
Timeframe: At Baseline and Week 52

Interventioncm/year (Least Squares Mean)
BMN 111 - 15 μg/kg1.71
Placebo0.13

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Change From Baseline in Height Z-score at Week 52

"Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention.~A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age.~A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age.~To conclude if the height Z score increases then this means the height deficit has decreased." (NCT03197766)
Timeframe: At baseline and Week 52

InterventionZ-Score (Least Squares Mean)
BMN 111 - 15 μg/kg0.27
Placebo-0.01

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Change From Baseline in Upper to Lower Segment Body Ratio at Week 52

Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks (NCT03197766)
Timeframe: At baseline and Week 52

InterventionRatio (Least Squares Mean)
BMN 111 - 15 μg/kg-0.03
Placebo-0.02

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Correlation Between Serum CNP and Follicle Stimulating Hormone and Luteinizing Hormone Levels in Groups 1 and 2

Correlations between serum CNP vs Follicle Stimulating Hormone(FSH), CNP vs Luteinizing Hormone(LH) levels in groups 1 and 2 (NCT04000815)
Timeframe: Second or Third Day of Menstruation

,
InterventionmIU/mL (Median)
Follicle Stimulating HormoneLuteinizing Hormone
Perimenopausal Women13.125.16
Reproductive Age Women5.285.71

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Serum C Type Natriuretic Peptide Levels

The comparison of serum levels of C type natriuretic peptide among different age groups (NCT04000815)
Timeframe: Second or Third Day of Menstruation

Interventionpg/ml (Median)
Reproductive Age Women43.68
Perimenopausal Women55.98
Postmenopausal Women116.36

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Correlation Between Serum CNP and Estradiol Levels in Groups 1 and 2

Correlation of CNP vs. Estradiol levels in reproductive age and perimenopausal women (NCT04000815)
Timeframe: Second or Third Day of Menstruation

Interventionpg/mL (Median)
Reproductive Age Women41
Perimenopausal Women22

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Correlation Between Serum CNP and Antral Follicle Count (AFC) in Groups 1 and 2

Correlation between serum CNP and antral follicle count (AFC) in groups 1 and 2 using Spearman test (NCT04000815)
Timeframe: Second or Third Day of Menstruation

Interventionfollicles (Mean)
Reproductive Age Women14.2
Perimenopausal Women8.33

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Serum Tiroid Stimulating Hormone of PCOS and Healthy Women

serum tiroid stimulating hormone of PCOS and healthy women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

InterventionmIU/L (Median)
Women With Polycystic Ovary Syndrome1.61
Healthy Women of Reproductive Age1.47

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High Density Lipoprotein and Low Density Lipoprotein Levels of Participants

High density lipoprotein and low density lipoprotein levels of participants were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation-morning fasting

,
Interventionmg/dL (Mean)
High density lipoproteinLow density lipoprotein
Healthy Women of Reproductive Age62.1592.92
Women With Polycystic Ovary Syndrome53.8298.50

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Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women

Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionnmol/L (Median)
Women With Polycystic Ovary Syndrome30.4
Healthy Women of Reproductive Age59.4

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Serum Prolactin Levels of PCOS and Healthy Women

serum prolactin levels of PCOS and healthy women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionng/mL (Mean)
Women With Polycystic Ovary Syndrome17.21
Healthy Women of Reproductive Age16.80

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Serum Insulin Levels of Participants

Serum Insulin Levels of Participants were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation-morning fasting

InterventionmU/L (Median)
Women With Polycystic Ovary Syndrome7.10
Healthy Women of Reproductive Age7.10

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Serum Free Testosterone Levels of PCOS and Healthy Women

Serum Free Testosterone Levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionpg/mL (Mean)
Women With Polycystic Ovary Syndrome1.71
Healthy Women of Reproductive Age1.12

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Serum Estradiol Levels of PCOS and Healthy Women

Serum Estradiol levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionpg/mL (Median)
Women With Polycystic Ovary Syndrome31
Healthy Women of Reproductive Age36.5

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Serum Dehydroepiandrosterone Sulfate (DHEAS) Levels of PCOS and Healthy Women

Serum dehydroepiandrosterone sulfate (DHEAS) Levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionµg/dL (Median)
Women With Polycystic Ovary Syndrome304.55
Healthy Women of Reproductive Age299.95

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Serum CNP Levels of PCOS and Healthy Participants

The comparison of serum levels of C type natriuretic peptide among PCOS and healthy women (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionpg/ml (Median)
Women With Polycystic Ovary Syndrome110
Healthy Women of Reproductive Age57

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Serum Androstenedione Levels of PCOS and Healthy Women

Serum Androstenedione Levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionng/dL (Mean)
Women With Polycystic Ovary Syndrome148.89
Healthy Women of Reproductive Age84.66

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Roc Curve of CNP

We made a cut off value estimation for the diagnosis of PCOS by serum CNP levels using Receiver operator characteristics. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the CNP for diagnosing PCOS (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionprobability (Number)
All Participants0.706

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Free Androgen Index of Participants

Free androgen index of participants were compared. It was calculated with the formula 100XTotal testosterone/Sex hormone binding globulin (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Intervention% of T testosterone per SHBG (Mean)
Women With Polycystic Ovary Syndrome4.39
Healthy Women of Reproductive Age1.55

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Homeostatic Model Assessment of Insulin Resistance of Participants

homeostatic model assessment of insulin resistance of participants were compared. The calculation was made with formula Glucose X Insulin/405. (NCT04006171)
Timeframe: Second or Third Day of Menstruation-morning fasting

InterventionHOMA-IR Index (Median)
Women With Polycystic Ovary Syndrome1.50
Healthy Women of Reproductive Age1.45

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Serum Glucose, Total Cholesterol and Triglycerides Levels of Participants

Serum glucose, total cholesterol and triglycerides levels of participants were compared (NCT04006171)
Timeframe: Second or third day of menstruation and morning fasting

,
Interventionmg/dL (Median)
Total cholesteroltriglyceridesGlucose
Healthy Women of Reproductive Age1717789
Women With Polycystic Ovary Syndrome1647888.5

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Comparison of FSH and LH of PCOS and Healthy Women

Serum FSH and LH of PCOS and healthy women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

,
InterventionmIU/mL (Median)
Follicle Stimulating HormoneLuteinizing Hormone
Healthy Women of Reproductive Age4.975.36
Women With Polycystic Ovary Syndrome4.74.23

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Serum Total Testosterone Levels of PCOS and Healthy Women

Serum Total Testosterone Levels of PCOS and Healthy Women were compared (NCT04006171)
Timeframe: Second or Third Day of Menstruation

Interventionnmol/L (Mean)
Women With Polycystic Ovary Syndrome1.38
Healthy Women of Reproductive Age0.92

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