Page last updated: 2024-10-20

pyruvic acid and Anemia, Sickle Cell

pyruvic acid has been researched along with Anemia, Sickle Cell in 3 studies

Pyruvic Acid: An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)
pyruvic acid : A 2-oxo monocarboxylic acid that is the 2-keto derivative of propionic acid. It is a metabolite obtained during glycolysis.

Anemia, Sickle Cell: A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.

Research Excerpts

ExcerptRelevanceReference
" After daily dosing of etavopivat over 5 consecutive days in NHPs, ATP was increased by 38% from baseline."1.72Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease. ( Drake, A; Fessler, R; Forsyth, S; Fulzele, K; Guichard, S; Kalfa, TA; Konstantinidis, DG; Marshall, CG; Ribadeneira, MD; Schroeder, P; Seu, KG; Wilker, E, 2022)

Research

Studies (3)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's0 (0.00)24.3611
2020's3 (100.00)2.80

Authors

AuthorsStudies
Schroeder, P1
Fulzele, K1
Forsyth, S1
Ribadeneira, MD1
Guichard, S1
Wilker, E1
Marshall, CG1
Drake, A1
Fessler, R1
Konstantinidis, DG1
Seu, KG1
Kalfa, TA1
Xu, JZ1
Conrey, A1
Frey, I1
Gwaabe, E1
Menapace, LA1
Tumburu, L1
Lundt, M1
Lequang, T1
Li, Q1
Glass, K1
Dunkelberger, EB1
Iyer, V1
Mangus, H1
Kung, C1
Dang, L1
Kosinski, PA1
Hawkins, P1
Jeffries, N1
Eaton, WA1
Lay Thein, S1
Little, JA1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Oral Doses of AG-348 in Subjects With Stable Sickle Cell Disease[NCT04000165]Early Phase 117 participants (Actual)Interventional2019-07-11Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Number Participants With Increase of ≥ 1 g/dL in Hemoglobin

To assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by defined as a ≥ 1 g/dL increase in hemoglobin at any dose level compared to baseline. (NCT04000165)
Timeframe: 14 weeks

InterventionParticipants (Count of Participants)
AG-348 in Participants With Sickle Cell Disease9

Number Participants With Serious Adverse Events That Were Possibly Drug-related Serious Adverse Events

To assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) 5.0. (NCT04000165)
Timeframe: 14 weeks

InterventionParticipants (Count of Participants)
AG-348 in Participants With Sickle Cell Disease2

Change in Absolute Reticulocyte Count at Each Dose Level of AG-348

To assess change in absolute reticulocyte count in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionK/mcL (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease196.44-20.97-20.72-44.99-34.1-13.778.1

Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348

To assess change in aspartate aminotransferase (AST) in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionU/L (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease33.88-3.31-3.37-2-3.54-2.493.02

Change in Fetal Hemoglobin at Each Dose Level of AG-348

To assess the change in fetal hemoglobin (HbF) in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionPercent HbF (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease20.39-0.42-1.02-1.31-0.340.190.81

Change in Hemoglobin at Each Dose Level of AG-348

To assess change in hemoglobin in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

Interventiong/dL (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease8.730.340.761.190.920.340.37

Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348

To assess change in lactic acid dehydrogenase (LDH) in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionU/L (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease348.4-7.81-39.94-25.31-37.8920.6330.72

Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348

To assess change in mean corpuscular volume (MCV) in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionfL (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease103.32-0.50.520.421.98-0.25-0.64

Change in Total Bilirubin at Each Dose Level of AG-348

To assess change in total bilirubin in stable sickle cell disease participants at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

Interventionmg/dL (Mean)
Baseline5 mg dose of AG-34820 mg dose AG-34850 mg dose AG-348100 mg dose AG-348End Of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease1.82-0.19-0.56-0.77-0.87-0.190.1

Number Participants With Most Common Reported Drug Related Adverse Events

To assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) 5.0. (NCT04000165)
Timeframe: 14 weeks

InterventionParticipants (Count of Participants)
InsomniaArthralgiaHypertension
AG-348 in Participants With Sickle Cell Disease633

Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348

Measure percent change from baseline in oxygen binding p50 value at each dose level of AG-348 (NCT04000165)
Timeframe: 14 weeks

InterventionPercent Change (Mean)
5 mg Dose AG-34820 mg Dose AG-34850 mg Dose AG-348100 mg Dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease0.5-2.09-3.84-4.887.9710.79

Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348

To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of 2,3-DPG at each dose level of AG-348. (NCT04000165)
Timeframe: 14 weeks

Interventionpercent change (Mean)
5 mg Dose AG-34820 mg Dose AG-34850 mg Dose AG-348100 mg Dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease-3.74-16.08-23.49-24.131.979.11

Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348

To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of adenosine triphosphate (ATP) at each dose level of AG-348. (NCT04000165)
Timeframe: 14 weeks

Interventionpercent change (Mean)
5 mg Dose AG-34820 mg Dose AG-34850 mg Dose AG-348100 mg Dose AG-348End of Taper Dose AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease13.6826.9533.4339.8415.5112.03

Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348

Measure percent change in Time (mins) at which 50% of red blood cells are sickled (t50) Value at Each Dose Level of AG-348 (NCT04000165)
Timeframe: 14 weeks

Interventionpercent change (Mean)
5 mg Dose AG-34820 mg Dose AG-34850 mg Dose AG-348100 mg Dose AG-348End of Taper AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease-0.4610.197.1113.98-11.381.67

Percent Change of PK-R at Each Dose Level of AG-348

To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of PK-R at each dose level of AG-348. (NCT04000165)
Timeframe: 14 weeks

Interventionpercent change (Mean)
5 mg Dose AG-34820 mg Dose AG-34850 mg Dose AG-348100 mg Dose AG-348End of Taper AG-348End of Study AG-348
AG-348 in Participants With Sickle Cell Disease-6.89-2.82-10.66-28.99-8.38-16.47

Trials

1 trial available for pyruvic acid and Anemia, Sickle Cell

ArticleYear
A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease.
    Blood, 2022, 11-10, Volume: 140, Issue:19

    Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Adult; Anemia, Sickle Cell; Hemoglobins; Humans; Pyr

2022

Other Studies

2 other studies available for pyruvic acid and Anemia, Sickle Cell

ArticleYear
Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease.
    The Journal of pharmacology and experimental therapeutics, 2022, Volume: 380, Issue:3

    Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Anemia, Sickle Cell; Animals; Erythrocytes; Hemoglob

2022
RBC, heal thyself: PK activators in SCD.
    Blood, 2022, 11-10, Volume: 140, Issue:19

    Topics: Anemia, Sickle Cell; Humans; Piperazines; Pyruvate Kinase; Pyruvic Acid

2022