Bioavailability Study Comparing 10 mg Amlodipine Besylate Orally Disintegrating Tablets (ODT) And 10 mg Amlodipine Besylate Capsules

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01177293
• Collaborator: Aurobindo Pharma Ltd (Industry), Trident Life Sciences Ltd. (Industry)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 4.6

Study Details

Study Description

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 capsule.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Amlodipine - reference; Drug: Amlodipine ODT - test	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Phase 1, Open-Label, Randomized, Single-Dose, 2-Treatment, 2-Period Crossover Bioavailability Study Comparing 10 Mg Amlodipine Besylate Orally Disintegrating Tablets, Manufactured By Aurobindo Pharma Ltd., India To 10 Mg Amlodipine Besylate Capsules, Manufactured By Pfizer France Under Fasted Conditions
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: treatment A - reference w/ water	Drug: Amlodipine - reference; Amlodipine capsule, 10 mg, single dose, with water
Experimental: Treatment B - ODT (test) w/o water	Drug: Amlodipine ODT - test; Amlodipine orally disintegrating tablet (ODT), 10 mg, single dose, without water

Outcome Measures

Primary Outcome Measures

1. 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-∞).

2. Area Under the Curve 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).

3. 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 Outcome Measures

1. 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]

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male and/or female literate 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 17.5 to 26.4 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Hydrabad	Andhra Pradesh	India	500 050

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Aurobindo Pharma Ltd
• Trident Life Sciences Ltd.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01177293
• Other Study ID Numbers: A0531096; 052-10
• First Posted: Aug 6, 2010
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: biological availability; bioavailability; amlodipine; orally disintegrating tablet; ODT; tablets
• Additional relevant MeSH terms: Amlodipine

Study Results

Participant Flow

Arm/Group Title	Amlodipine Capsule Then Amlodipine ODT	Amlodipine ODT Then Amlodipine Capsule
Arm/Group Description	Single oral dose amlodipine besylate 10 mg capsule in first intervention period and single oral dose of amlodipine besylate 10 mg oral disintegrating tablet (ODT) in second intervention period. A washout period of 14 days was maintained between each period.	Single oral dose amlodipine besylate 10 mg ODT in first intervention period and single oral dose of amlodipine besylate 10 mg capsule in second intervention period. A washout period of 14 days was maintained between each period.
Period Title: First Intervention Period
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0
Period Title: First Intervention Period
STARTED	7	7
COMPLETED	7	6
NOT COMPLETED	0	1
Period Title: First Intervention Period
STARTED	7	6
COMPLETED	7	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Includes groups randomized to receive any treatment first (amlodipine capsule first and amlodipine ODT first).
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.00 (6.36)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	14 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)]
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amlodipine 10 mg Capsule	Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).	Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
Measure Participants	12	13
Geometric Mean (Full Range) [hr*ng/mL]	401.655	360.619

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg Capsule, Amlodipine 10 mg ODT
	Comments	A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1155 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.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Natural log transformed AUC[0- ∞] of amlodipine was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric means ratio
	Estimated Value	89.78
	Confidence Interval	(2-Sided) 90%; 82.74 to 97.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amlodipine 10 mg Capsule	Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).	Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
Measure Participants	12	13
Geometric Mean (Full Range) [hr*ng/mL]	331.300	330.394

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg Capsule, Amlodipine 10 mg ODT
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Natural log transformed AUClast of amlodipine was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	99.73
	Confidence Interval	(2-Sided) 90%; 85.10 to 116.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amlodipine 10 mg Capsule	Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).	Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
Measure Participants	12	13
Geometric Mean (Full Range) [ng/mL]	6.427	5.571

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg Capsule, Amlodipine 10 mg ODT
	Comments	A sample size of 12 completers provided 90% confidence intervals for the difference between treatment of +/-0.1278 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.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Natural log transformed Cmax of amlodipine was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric means ratio
	Estimated Value	86.67
	Confidence Interval	(2-Sided) 90%; 79.57 to 94.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amlodipine 10 mg Capsule	Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).	Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
Measure Participants	12	13
Median (Full Range) [hr]	8.00	10.00

5. Secondary Outcome

Title	Plasma Decay Half-life (t1/2)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amlodipine 10 mg Capsule	Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).	Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
Measure Participants	12	13
Mean (Standard Deviation) [hr]	51.374 (12.912)	45.120 (4.921)

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Amlodipine 10 mg Capsule		Amlodipine 10 mg ODT
Arm/Group Description	Single oral dose of amlodipine 10 mg capsule (Treatment A [Reference]).		Single oral dose of amlodipine 10 mg ODT (Treatment B [Test]).
All Cause Mortality
	Amlodipine 10 mg Capsule		Amlodipine 10 mg ODT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Amlodipine 10 mg Capsule		Amlodipine 10 mg ODT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Amlodipine 10 mg Capsule		Amlodipine 10 mg ODT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.