Trial Outcomes & Findings for Bioequivalence of Losartan and Hydrochlorothiazide (HCTZ) Combination Tablet and Coadministration of Its Components (0954A-306) (NCT NCT00953680)
NCT ID: NCT00953680
Last Updated: 2022-02-09
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
77 participants
Primary outcome timeframe
0 to 36 Hours Post Dose
Results posted on
2022-02-09
Participant Flow
Participant milestones
| Measure |
Losartan-HCTZ Combination Tablet/Losartan Tablet +HCTZ Capsule
Single dose losartan 100 mg and hydrochlorothiazide (HCTZ) 12.5 mg combination tablet then a single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
Losartan Tablet +HCTZ Capsule/Losartan-HCTZ Combination Tablet
Single dose losartan 100 mg tablet + hydrochlorothiazide (HCTZ) 12.5 mg capsule then a single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
|---|---|---|
|
Period 1
STARTED
|
38
|
39
|
|
Period 1
COMPLETED
|
38
|
38
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
|
Period 2
STARTED
|
38
|
38
|
|
Period 2
COMPLETED
|
38
|
38
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Losartan-HCTZ Combination Tablet/Losartan Tablet +HCTZ Capsule
Single dose losartan 100 mg and hydrochlorothiazide (HCTZ) 12.5 mg combination tablet then a single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
Losartan Tablet +HCTZ Capsule/Losartan-HCTZ Combination Tablet
Single dose losartan 100 mg tablet + hydrochlorothiazide (HCTZ) 12.5 mg capsule then a single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Bioequivalence of Losartan and Hydrochlorothiazide (HCTZ) Combination Tablet and Coadministration of Its Components (0954A-306)
Baseline characteristics by cohort
| Measure |
All Participants
n=77 Participants
All randomized patients
|
|---|---|
|
Age, Continuous
|
33.87 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=99 Participants
|
|
Height
|
166.81 Centimeters
n=99 Participants
|
|
Weight
|
73.01 kilograms
n=99 Participants
|
PRIMARY outcome
Timeframe: 0 to 36 Hours Post DosePopulation: Pharmacokinetic (PK) results included complete data from 75 of 77 subjects (with 1 replacement). Partial data from 1 subject were not analyzed. Plasma concentrations for another subject were undetectable following 1 treatment, with partial data excluded from analyses.
Outcome measures
| Measure |
Losartan-HCTZ Combination Tablet
n=75 Participants
single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
Losartan Tablet + HCTZ Capsule
n=75 Participants
Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
|---|---|---|
|
Area Under the Curve (AUC(0 to Infinity)) of Losartan
|
1018.1 ng*hr/mL
Standard Deviation 382.5
|
1024.9 ng*hr/mL
Standard Deviation 354.6
|
PRIMARY outcome
Timeframe: 36 Hours Post DosePopulation: Pharmacokinetic (PK) results included complete data from 75 of 77 subjects (with 1 replacement). Partial data from 1 subject were not analyzed. Plasma concentrations for another subject were undetectable following 1 treatment, with partial data excluded from analyses.
Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing.
Outcome measures
| Measure |
Losartan-HCTZ Combination Tablet
n=75 Participants
single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
Losartan Tablet + HCTZ Capsule
n=75 Participants
Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) for Losartan
|
532.7 ng/mL
Standard Deviation 334.9
|
637.9 ng/mL
Standard Deviation 425.3
|
PRIMARY outcome
Timeframe: 0 to 30 Hours Post DosePopulation: Pharmacokinetic (PK) results included complete data from 75 of 77 subjects (with 1 replacement). Partial data from 1 subject were not analyzed. Plasma concentrations for another subject were undetectable following 1 treatment, with partial data excluded from analyses.
Plasma Area Under the Curve, a measure of drug exposure following dosing
Outcome measures
| Measure |
Losartan-HCTZ Combination Tablet
n=20 Participants
single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
Losartan Tablet + HCTZ Capsule
n=20 Participants
Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
|---|---|---|
|
Area Under the Curve (AUC(0 to Infinity)) of HCTZ
|
462.08 ng*hr/mL
Standard Deviation 144.72
|
499.90 ng*hr/mL
Standard Deviation 133.46
|
PRIMARY outcome
Timeframe: 30 Hours Post DosePopulation: Pharmacokinetic (PK) results were based on data from the 20 subjects who had blood drawn for the HCTZ assay. These 20 subjects were selected as the first 10 subjects from each treatment sequence who completed both periods of the study.
Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing
Outcome measures
| Measure |
Losartan-HCTZ Combination Tablet
n=20 Participants
single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
Losartan Tablet + HCTZ Capsule
n=20 Participants
Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of HCTZ Following Single Dose Administration of Losartan/HCTZ or Losartan and HCTZ
|
76.15 ng/mL
Standard Deviation 39.55
|
81.76 ng/mL
Standard Deviation 31.05
|
Adverse Events
Losartan-HCTZ Combination Tablet/Losartan Tablet +HCTZ Capsule
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Losartan Tablet +HCTZ Capsule/Losartan-HCTZ Combination Tablet
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Losartan-HCTZ Combination Tablet/Losartan Tablet +HCTZ Capsule
n=76 participants at risk；n=38 participants at risk
Single dose losartan 100 mg and hydrochlorothiazide (HCTZ) 12.5 mg combination tablet then a single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule
|
Losartan Tablet +HCTZ Capsule/Losartan-HCTZ Combination Tablet
n=77 participants at risk；n=39 participants at risk
losartan 100 mg tablet + hydrochlorothiazide (HCTZ) 12.5 mg capsule then a single dose losartan 100 mg and HCTZ 12.5 mg combination tablet
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
1.3%
1/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
1/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
1.3%
1/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
|
Investigations
Alanine Aminotransferase Increased
|
1.3%
1/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
0.00%
0/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
|
Investigations
Aspartate Aminotransferase Increased
|
1.3%
1/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
0.00%
0/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
|
Nervous system disorders
Dizziness
|
6.6%
5/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
3.9%
3/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
|
Nervous system disorders
Headache
|
10.5%
8/76
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
7.8%
6/77
Serious Adverse Events are reported by treatment group (Combination/Tablet+Capsule \[N=38\] or Tablet+Capsule/Combination \[N=39\]). For Other Adverse Events, the Combination/Tablet+Capsule group includes all subjects who received Combination Tablet (N=76) and the Tablet+Capsule/Combination group includes all subjects who received Tablet+Capsule (N=77)
|
Additional Information
Executive Vice President, Clinical and Quantitative Sciences
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER