Healthy Volunteers
Conditions
Keywords
biological availability, bioavailability, amlodipine, orally disintegrating tablet, ODT, tablets
Brief summary
This study is being performed to determine the bioavailability, or extent of absorption into the body, of a 10 mg amlodipine besylate orally disintegrating tablet (ODT) as compared to the bioavailability of a 10 mg amlodipine besylate (non-ODT) tablet.
Interventions
10 mg tablet, single dose, with water
10 mg orally disintegrating tablet (ODT), single dose, with water
Sponsors
Aurobindo Pharma Ltd
Trident Life Sciences Ltd.
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). * Body Mass Index (BMI) of 18 to 26 kg/m2; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * A positive urine drug screen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose | AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). |
| AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose | Area under the plasma concentration-time curve from time zero (pre-dose) to the time of the last measurable concentration (AUClast). |
| Maximum Observed Plasma Concentration (Cmax) | 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose | — |
| Plasma Decay Half-Life (t1/2) | 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants randomized to any treatment.(Amlodipine tablet first, amlodipine ODT first, and amlodipine ODT without water first). | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout Period I (of 16 Days) | Lost to Follow-up | 1 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 27.22 years STANDARD_DEVIATION 7.22 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Time frame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose
Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Amlodipine 10mg Tablet With Water (Reference Product A) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 307.225 hr*ng/mL |
| Amlodipine 10 mg ODT With Water (Test Product B) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 324.324 hr*ng/mL |
| Amlodipine 10 mg ODT Without Water (Test Product C) | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 330.411 hr*ng/mL |
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1036 on the natural log scale for AUCinf with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1234 for loge AUCinf.90% CI: [98.09, 113.61]
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1036 on the natural log scale for AUCinf with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1234 for loge AUCinf.90% CI: [99.98, 115.69]
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1036 on the natural log scale for AUCinf with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1234 for loge AUCinf.90% CI: [94.7, 109.6]
Primary
AUC From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time curve from time zero (pre-dose) to the time of the last measurable concentration (AUClast).
Time frame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Amlodipine 10mg Tablet With Water (Reference Product A) | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 275.302 hr*ng/mL |
| Amlodipine 10 mg ODT With Water (Test Product B) | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 285.974 hr*ng/mL |
| Amlodipine 10 mg ODT Without Water (Test Product C) | AUC From Time Zero to Last Quantifiable Concentration (AUClast) | 287.035 hr*ng/mL |
90% CI: [97.27, 110.94]
90% CI: [97.67, 111.3]
90% CI: [94.02, 107.15]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Amlodipine 10mg Tablet With Water (Reference Product A) | Maximum Observed Plasma Concentration (Cmax) | 5.201 ng/mL |
| Amlodipine 10 mg ODT With Water (Test Product B) | Maximum Observed Plasma Concentration (Cmax) | 5.117 ng/mL |
| Amlodipine 10 mg ODT Without Water (Test Product C) | Maximum Observed Plasma Concentration (Cmax) | 4.952 ng/mL |
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1146 on the natural log scale for Cmax with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1366 for loge Cmax.90% CI: [91.05, 106.33]
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1146 on the natural log scale for Cmax with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1366 for loge Cmax.90% CI: [88.16, 102.84]
Comparison: A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1146 on the natural log scale for Cmax with 90% coverage probability. These calculations were based on estimates of within-participant standard deviations of 0.1366 for loge Cmax.90% CI: [89.58, 104.54]
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 10mg Tablet With Water (Reference Product A) | Plasma Decay Half-Life (t1/2) | 44.004 hr | Standard Deviation 13.759 |
| Amlodipine 10 mg ODT With Water (Test Product B) | Plasma Decay Half-Life (t1/2) | 46.698 hr | Standard Deviation 14.739 |
| Amlodipine 10 mg ODT Without Water (Test Product C) | Plasma Decay Half-Life (t1/2) | 49.869 hr | Standard Deviation 19.638 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, 96, 120, and 168 hours post dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amlodipine 10mg Tablet With Water (Reference Product A) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 8.00 hr |
| Amlodipine 10 mg ODT With Water (Test Product B) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 10.00 hr |
| Amlodipine 10 mg ODT Without Water (Test Product C) | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 13.00 hr |