A Bioequivalence Study Between Capozide Versus ACE-Hemmer-ratiopharm in Healthy Adult Participants Under Fasting Conditions

NCT04964050 | Withdrawn Phase 1

• 1 other identifier: 213049
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a bioequivalence study to compare Capozide (test product \[T\]) to ACE-Hemmer-ratiopharm (reference product\[R\]) produced by Ratiopharm GmbH Germany in healthy adult participants under fasting conditions. ACE-Hemmer-ratiopharm®is the registered trademark of Ratiopharm GmbH Germany.

Conditions

Healthy Volunteers

Keywords

ACE-Hemmer-Ratiopharm; Bioequivalence; Capozide; Captopril/Hydrochlorothiazide

Outcome Measures

Primary Outcomes (3)

• Maximum observed concentration (Cmax) of Captopril and Hydrochlorothiazide (HCTZ)

  Up to 3 weeks

• Area under the concentration-time curve from administration extrapolated to the last time of quantifiable concentration (AUC[0-t]) of Captopril and HCTZ

  Up to 3 weeks

• Area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-inf]) of Captopril and HCTZ

  Up to 3 weeks

Secondary Outcomes (7)

• Time to reach Cmax (Tmax) of Captopril and HCTZ

  Up to 3 weeks

• Terminal elimination halftime (t1/2) of Captopril and HCTZ

  Up to 3 weeks

• Terminal elimination rate constant (lambda-z) of Captopril and HCTZ

  Up to 3 weeks

• Percentage of AUC(0-inf) obtained by extrapolation (%AUCex) of Captopril and HCTZ

  Up to 3 weeks

• Number of participants with adverse events (AE) serious AEs

  Up to 3 weeks

Study Arms (3)

Treatment sequence TRR

EXPERIMENTAL

Participants will receive Capozide (T) in period 1 followed by ACE-Hemmer-Ratiopharm (R) in period 2 followed by ACE-Hemmer-Ratiopharm (R) in period 3.

Drug: Capozide; Drug: ACE-Hemmer-Ratiopharm

Treatment sequence RTR

EXPERIMENTAL

Participants will receive ACE-Hemmer-Ratiopharm (R) in period 1 followed by Capozide (T) in period 2 followed by ACE-Hemmer-Ratiopharm (R) in period 3.

Drug: Capozide; Drug: ACE-Hemmer-Ratiopharm

Treatment sequence RRT

EXPERIMENTAL

Participants will receive ACE-Hemmer-Ratiopharm (R) in period 1 followed by ACE-Hemmer-Ratiopharm (R) in period 2 followed Capozide (T) by in period 3.

Drug: Capozide; Drug: ACE-Hemmer-Ratiopharm

Interventions

Capozide DRUG

Capozide will be administered as per the treatment sequence.

Treatment sequence RRT; Treatment sequence RTR; Treatment sequence TRR

ACE-Hemmer-Ratiopharm DRUG

ACE-Hemmer-Ratiopharm will be administered as per the treatment sequence.

Treatment sequence RRT; Treatment sequence RTR; Treatment sequence TRR

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
• Participant does not have a known allergy to the drug under investigation, any of its ingredients or any other related drugs.
• Normal vital signs after up to 10 minutes resting in supine position or 2 minutes in sitting position: 100 millimeters of mercury (mmHg) less than or equal to (\<=) systolic blood pressure (SBP) \<130 mmHg; 70 mmHg \<= diastolic blood pressure (DBP) \<90 mmHg; 60 beats per minute (bpm) \<=Pulse rate (HR) \<=100 bpm.
• Normal standard 12-lead ECG after 10 minutes resting in supine position in the following ranges; 120 microseconds (ms)\<PR\<220 ms, QRS\<120 ms, QTc\<=450 ms, and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant.
• Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy participants; however serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) should not exceed 1.25 times the upper laboratory normal, and total bilirubin should not exceed the upper laboratory normal. Laboratory tests are performed not longer than two weeks before the initiation of the clinical study).
• Body weight on 45 kilograms (kg) or more and body mass index (BMI) within the range 18.5 -30 kg per meter square (kg/m\^2) (inclusive).
• Healthy Adult, male and female (woman of non-childbearing potential \[WONCBP\])
• Capable of giving signed informed consent.

You may not qualify if:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular or infectious disease, or signs of acute illness, lactose intolerance.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Blood donation, any volume, within 3 months.
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP greater than or equal to (\>=)30 mmHg within 3 minutes when changing from supine to standing position.
• Presence or history of drug hypersensitivity, participants with known hypersensitivity to any component of the investigational medicinal product (IMP) formulation or allergic disease diagnosed and treated by a physician. Participants who have previously demonstrated hypersensitivity to hydrochlorothiazide or to any sulfonamide-derived drugs.
• History of drug or alcohol abuse. History of regular alcohol consumption within one year of the study defined as: an average weekly intake of \>14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 milliliters \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Smoking regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study (occasional smoker can be enrolled). Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses \[average 100 mL\] per day).
• Use of any prescribed medication, over the counter (OTC) medicines or medicinal products during the last two weeks preceding the first dosing and until discharge from the study.
• Participation in a bioequivalence study or in a clinical study within the last 60 days before first study drug administration.
• Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis B core antibodies (anti-HBc Ab) if compound having possible immune activities, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
• Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Participants with a history of allergy or bronchial asthma or systemic lupus erythematosus.
• Participant who has results of laboratory tests which are outside the normal range or hemoglobin (Hb) or red blood cell (RBC) indices (mean corpuscular volume \[MCV\], mean corpuscular hemoglobin \[MCH\] and mean corpuscular hemoglobin concentration \[MCHC\]) with deviation outside 5% of the reference range. (Laboratory tests are performed not longer than two weeks before the initiation of the clinical study).
• Participants who have been on a specific/special diet during the 4 weeks before screening and who cannot agree to eat the set clinical food menu during the study.
• Participants that have a current active Coronavirus disease 2019 (COVID-19) infection, either laboratory confirmed or according to the investigator's medical judgement.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Interventions

captopril, hydrochlorothiazide drug combination

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 15, 2021
• Study Start: April 21, 2022
• Primary Completion: May 26, 2022
• Study Completion: May 26, 2022
• Last Updated: January 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.