adenine and Diarrhea

adenine has been researched along with Diarrhea in 21 studies

Diarrhea: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.

Research

Studies (21)

Authors

Clinical Trials (13)

Trial Overview

Trial Outcomes

Duration of Response (DOR) as Assessed by the Investigator

The DoR is defined as the time from the date of achieving the first CR, CRi, or PR to the date of progressive disease (PD) or death due to any cause, whichever occurred first. The CR, CRi, or PR are defined in the above outcome measure. For CLL/SLL, PD is defined as lympho >=50% increase from baseline with >= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or >= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of >=50% from baseline secondary to CLL or < 100,000/µL and worsening bone marrow or Hb decrease of > 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The DoR was estimated using Kaplan-Meier method. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1

Participants with DLTs in Phase 1 are reported. The DLT was defined as any of the following events unless the adverse event is clearly related to disease progression or the participant's current medical history and associated comorbidities: (1) Any Grade 3 or greater nonhematologic toxicity with the exceptions of alopecia and Grade 3 nausea, vomiting, and diarrhea that respond to supportive therapy; (2) Hematologic toxicities including Grade 4 neutropenia lasting more than 5 days, Grade 4 or Grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion, Grade 3 or greater febrile neutropenia (body temperature of 38.5 degrees Celsius or more), or Grade 4 anemia, unexplained by underlying disease; or (3) Dosing delay due to toxicity for > 7 consecutive days. (NCT02029443)
Timeframe: From Day 1 to Day 28 after first dose of study drug

Percentage of Participants With Objective Response (OR) as Assessed by the Investigator

For CLL/SLL, OR is defined as complete remission (CR), CR with incomplete marrow recovery (CRi), or partial remission (PR). CR: lymphocytes (lympho) <4×10^9/L, normocellular bone marrow (BM), normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophil count (ANC) >1.5×10^9/L, platelets >100×10^9/L, hemoglobin (Hb) >11g/dL. Cri: lympho <4×10^9/L, hypocellular BM, NLN, L/S, persistent anemia, hrombocytopenia, or neutropenia. PR: >=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (<5×10^9/L or >=50% decrease from baseline) and criteria of ANC/platelets/Hb per CR or >=50% improvement over baseline. Hematology result were without exogenous growth factors/transfusion. For RS, OR as CR or PR by Cheson et al. 2014 based on PET/CT scans and bone marrow. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms and PR: >=50% decrease in sum of the product diameter of 6 largest nodal masses and no new sites of disease. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Progression Free Survival (PFS) as Assessed by the Investigator

The PFS is defined as the time from the date of first dose of study drug to the date of first PD or death due to any cause, whichever occurred first. For CLL/SLL, PD is defined as lympho >= 50 % increase from baseline with >= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or >= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of >= 50 % from baseline secondary to CLL or < 100,000/µL and worsening bone marrow or Hb decrease of > 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The PFS was estimated using Kaplan-Meier method. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Apparent Oral Clearance (CL/F) of Acalabrutinib

The CL/F of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Apparent Volume of Distribution (Vz/F) of Acalabrutinib

The Vz/F of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib

The AUC0-6 of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib

The AUC0-inf of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib

The AUC0-last of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib

The Cmax of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Number of Participants With Clinically Abnormal Vital Signs Reported as TEAEs

Participants with clinically abnormal vital signs (blood pressure, respiratory rate, pulse rate, or body temperature) reported as TEAEs are reported. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More

Participants with clinically important laboratory abnormalities with CTCAE Grade 3 or more are reported. Laboratory analysis included hematology, clinical chemistry, amylase, lipase, cardiac troponin I, hepatitis B and C testing, and urinalysis. The CTCAE version 4.03 is a descriptive terminology is used for AE reporting. The CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Treatment Emergent Events of Clinical Interest (ECI)

The treatment emergent ECI included the events identified based on preclinical findings, emerging data from clinical studies relating to acalabrutinib, and pharmacological effects of approved Bruton's tyrosine kinase (BTK) inhibitors and reported after the first dose of the study drug. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Terminal Elimination Half-life (t1/2) of Acalabrutinib

The t1/2 of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Terminal Elimination Rate Constant (λz) of Acalabrutinib

The λz of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Time of Maximum Plasma Concentration (Tmax) of Acalabrutinib

The Tmax of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Death Event

All death events are due to AE, progressive disease, and other reasons. (NCT01109069)
Timeframe: 30 days after last dose of study drug

Number of Subjects With Adverse Events

Subjects were to receive ibrutinib once daily at the dose level the subject was receiving in the parent study until disease progression or unacceptable toxicity. The study included Screening, Treatment (from the first dose until study drug discontinuation), and Follow-up Phases. (NCT01109069)
Timeframe: 30 days after last dose of study drug, continue up to 6 months

Progressive Disease (PD)

A progressive disease confirmed by a CT scan. (NCT01109069)
Timeframe: 30 days after last dose of study drug, continue up to 6 months

Food Effect Cohort Assessments

Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose. (NCT01105247)
Timeframe: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.

Number of Participants With Treatment Emergent Adverse Events (AEs)

Number of participants who had experienced at least one treatment emergent AEs. (NCT01105247)
Timeframe: From first dose to within 30 days of last dose of PCI-32765

Percentage of Participants Achieving Response

Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. (NCT01105247)
Timeframe: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

Progression Free Survival Rate at 24 Months

Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size. (NCT01105247)
Timeframe: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

OS (Overall Survival)

OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm (NCT01578707)
Timeframe: OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up

Overall Response Rate (ORR) by Independent Review Committee (IRC)

Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013 (NCT01578707)
Timeframe: About 18 months after the first subject was enrolled

Overall Response Rate (ORR) by Investigator

Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013

The primary objective of this study was to evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) according to 2008 IWCLL guidelines. (NCT01578707)
Timeframe: Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.

Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up

Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

Rate of Sustained Hemoglobin and Platelet Improvement

Proportion of subjects with hemoglobin (HgB) increase >=20 g/L and platelet (PLT) increase >=50% over baseline continuously for >=56 days without blood transfusions or growth factors. (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

ORR (Overall Response Rate)

ORR is defined as the proportion of subjects who achieved complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR per IRC assessment. Response criteria are as outlined in the International Workshop on CLL (iwCLL) 2008 criteria with the 2012 iwCLL modification stating that treatment-related lymphocytosis in the setting of improvement in other parameters was not considered as PD and the 2013 iwCLL clarification of criteria for a partial response to therapy. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Overall Survival (OS)

OS is calculated for all randomized subjects as the duration of time from the date of randomization to the date of death due to any cause or the date last known alive for subjects who were not known to have died at study closure. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

PFS (Progression Free Survival)

"The primary objective of this study was to evaluate the efficacy of Ibrutinib compared with Chlorambucil based on the independent review committee (IRC) assessment of PFS~Progressive disease according to 2008 IWCLL guidelines was defined as:~Group A~Lymphadenopathy, increase ≥50%~Hepatomegaly, increase ≥50%~Splenomegaly, increase ≥50%~Blood lymphocytes, increase ≥ 50% over baseline~Group B~Platelets counts, decrease of ≥ 50% from baseline secondary to CLL~Hemoglobin, decrease of > 2 g/dL from baseline secondary to CLL" (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Hemoglobin Improvement

The proportion of subjects who achieved Hemoglobin >11 g/dL or increase ≥ 2 g/dL over baseline and persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Hemoglobin Improvement in Subjects With Baseline Anemia

In randomized subjects with baseline hemoglobin ≤ 11 g/dL, the proportion of subjects who achieved Hemoglobin >11 g/dL or increase ≥ 2 g/dL over baseline persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Platelet Improvement

The proportion of subjects who achieved platelet >100 x 10^9/L or increase ≥50% over baseline and persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Platelet Improvement in Subjects With Baseline Thrombocytopenia

In randomized subjects with baseline platelet ≤ 100 x 10^9/L, the proportion of subjects who achieved platelet >100 x 10^9/L or increase ≥50% over baseline persisted continuously for ≥56 days (8 wee without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with cutoff date of 4 May 2015. The median follow-up time is 18 month.

Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab

Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project). (NCT03689894)
Timeframe: 6 weeks, 3 months, and 6 months after initiation of treatment

Reviews

6 reviews available for adenine and Diarrhea

Trials

9 trials available for adenine and Diarrhea

Other Studies

6 other studies available for adenine and Diarrhea