Hypertension
Conditions
Brief summary
This study will evaluate the bioequivalence of the losartan/hydrochlorothiazide (HCTZ) combination tablet and coadministration of losartan and hydrochlorothiazide.
Interventions
DRUGlosartan potassium (+) hydrochlorothiazide (HCTZ)
Single dose losartan 100 mg/HCTZ 12.5 mg combination tablet in one of two treatment periods.
DRUGlosartan potassium
Single dose losartan 100 mg tablet in one of two treatment periods.
Single dose HCTZ 12.5 mg capsule in one of two treatment periods.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is a healthy male or female between the ages of 18 and 45 years of age * Subject does not smoke
Exclusion criteria
* Subject has a history of any illness that might pose additional risk to participation or confound the results of the study * Subject has a history of hepatitis B or C or significant drug allergies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC(0 to Infinity)) of Losartan | 0 to 36 Hours Post Dose | — |
| Peak Plasma Concentration (Cmax) for Losartan | 36 Hours Post Dose | Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing. |
| Area Under the Curve (AUC(0 to Infinity)) of HCTZ | 0 to 30 Hours Post Dose | Plasma Area Under the Curve, a measure of drug exposure following dosing |
| Peak Plasma Concentration (Cmax) of HCTZ Following Single Dose Administration of Losartan/HCTZ or Losartan and HCTZ | 30 Hours Post Dose | Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All randomized patients | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 33.87 years |
| Height | 166.81 Centimeters |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 31 Participants |
| Weight | 73.01 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 76 | 10 / 77 |
| serious Total, serious adverse events | 0 / 38 | 0 / 39 |
Outcome results
Primary
Area Under the Curve (AUC(0 to Infinity)) of HCTZ
Plasma Area Under the Curve, a measure of drug exposure following dosing
Time frame: 0 to 30 Hours Post Dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan-HCTZ Combination Tablet | Area Under the Curve (AUC(0 to Infinity)) of HCTZ | 462.08 ng*hr/mL | Standard Deviation 144.72 |
| Losartan Tablet + HCTZ Capsule | Area Under the Curve (AUC(0 to Infinity)) of HCTZ | 499.90 ng*hr/mL | Standard Deviation 133.46 |
Comparison: Least-Squares Mean Ratio (A/B); A= Single dose losartan 100 mg-HCTZ 12.5 mg combination tablet; B= Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule90% CI: [0.825, 1.035]
Primary
Area Under the Curve (AUC(0 to Infinity)) of Losartan
Time frame: 0 to 36 Hours Post Dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan-HCTZ Combination Tablet | Area Under the Curve (AUC(0 to Infinity)) of Losartan | 1018.1 ng*hr/mL | Standard Deviation 382.5 |
| Losartan Tablet + HCTZ Capsule | Area Under the Curve (AUC(0 to Infinity)) of Losartan | 1024.9 ng*hr/mL | Standard Deviation 354.6 |
Comparison: Least-Squares Mean Ratio (A/B); A= Single dose losartan 100 mg-HCTZ 12.5 mg combination tablet; B= Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule90% CI: [0.95, 1.039]
Primary
Peak Plasma Concentration (Cmax) for Losartan
Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing.
Time frame: 36 Hours Post Dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan-HCTZ Combination Tablet | Peak Plasma Concentration (Cmax) for Losartan | 532.7 ng/mL | Standard Deviation 334.9 |
| Losartan Tablet + HCTZ Capsule | Peak Plasma Concentration (Cmax) for Losartan | 637.9 ng/mL | Standard Deviation 425.3 |
Comparison: Least-Squares Mean Ratio (A/B); A= Single dose losartan 100 mg-HCTZ 12.5 mg combination tablet; B= Single dose losartan 100-mg tablet + HCTZ 12.5 mg capsule90% CI: [0.749, 0.931]
Primary
Peak Plasma Concentration (Cmax) of HCTZ Following Single Dose Administration of Losartan/HCTZ or Losartan and HCTZ
Peak Plasma Concentration (Cmax), or maximal concentration of drug following dosing
Time frame: 30 Hours Post Dose
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan-HCTZ Combination Tablet | 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 |
| Losartan Tablet + HCTZ Capsule | Peak Plasma Concentration (Cmax) of HCTZ Following Single Dose Administration of Losartan/HCTZ or Losartan and HCTZ | 81.76 ng/mL | Standard Deviation 31.05 |
Comparison: Least-Squares Mean Ratio (A/B); A= Single dose losartan 100 mg-HCTZ 12.5 mg combination tablet; B= Single dose losartan 100 mg tablet + HCTZ 12.5 mg capsule90% CI: [0.836, 1.037]