Bioavailability Study Comparing 10 Mg Amlodipine Besylate Orally Disintegrating Tablet (ODT) And 10 Mg Amlodipine Besylate Tablets

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01138826
• Collaborator: Aurobindo Pharma Ltd (Industry), Trident Life Sciences Ltd. (Industry)
• Enrollment: 18
• Location: 1
• Arms: 3
• Duration (Months): 1
• Patients Per Site Per Month: 17.7

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 (non-ODT) tablet.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Phase 1, Open-Label, Randomized, Single-Dose, 3-Treatment, 6-Sequence, 3-Period Crossover Bioavailability Study Comparing 10 Mg Amlodipine Besylate Orally Disintegrating Tablets, Manufactured By Aurobindo Pharma Ltd., India To Amlodipine Besylate 10 Mg Tablets Manufactured by Pfizer Illertissen, Germany Under Fasted Conditions
• Study Start Date: May 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; 10 mg tablet, single dose, with water
Experimental: Treatment B - ODT (test) w/ water	Drug: Amlodipine ODT - test; 10 mg orally disintegrating tablet (ODT), single dose, with water
Experimental: Treatment C - ODT (test) w/o water	Drug: Amlodipine ODT - test; 10 mg orally disintegrating tablet (ODT), 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. 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).

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 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.

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: NCT01138826
• Other Study ID Numbers: A0531095; 051-10
• First Posted: Jun 7, 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 Tablet,Amlodipine ODT,Amlodipine ODT Without Water	Amlodipine Tablet,Amlodipine ODT Without Water,Amlodipine ODT	Amlodipine ODT,Amlodipine ODT Without Water,Amlodipine Tablet	Amlodipine ODT,Amlodipine Tablet,Amlodipine ODT Without Water	Amlodipine ODT Without Water,Amlodipine Tablet,Amlodipine ODT	Amlodipine ODT Without Water,Amlodipine ODT,Amlodipine Tablet
Arm/Group Description	Single oral dose amlodipine 10 mg tablet in first intervention period; followed by single oral dose of amlodipine 10 mg oral disintegrating tablet (ODT) in second intervention period; and single oral dose of amlodipine 10 mg ODT without water in third intervention period. A washout period of 16 days was maintained between each period.	Single oral dose amlodipine 10 mg tablet in first intervention period; followed by single oral dose of amlodipine 10 mg ODT without water in second intervention period; and single oral dose of amlodipine 10 mg ODT in third intervention period. A washout period of 16 days was maintained between each period.	Single oral dose amlodipine 10 mg ODT in first intervention period; followed by single oral dose of amlodipine 10 mg ODT without water in second intervention period; and single oral dose of amlodipine 10 mg tablet in third intervention period. A washout period of 16 days was maintained between each period.	Single oral dose amlodipine 10 mg ODT in first intervention period; followed by single oral dose of amlodipine 10 mg tablet in second intervention period; and single oral dose of amlodipine 10 mg ODT without water in third intervention period. A washout period of 16 days was maintained between each period.	Single oral dose amlodipine 10 mg ODT without water in first intervention period; followed by single oral dose of amlodipine 10 mg tablet in second intervention period; and single oral dose of amlodipine 10 mg ODT in third intervention period. A washout period of 16 days was maintained between each period.	Single oral dose amlodipine 10 mg ODT without water in first intervention period; followed by single oral dose of amlodipine 10 mg ODT in second intervention period; and single oral dose of amlodipine 10 mg tablet in third intervention period. A washout period of 16 days was maintained between each period.
Period Title: First Intervention Period
STARTED	3	3	3	3	3	3
COMPLETED	3	3	3	3	3	3
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention Period
STARTED	3	3	3	3	3	3
COMPLETED	2	2	3	3	2	3
NOT COMPLETED	1	1	0	0	1	0
Period Title: First Intervention Period
STARTED	2	2	3	3	2	3
COMPLETED	2	2	3	3	2	3
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention Period
STARTED	2	2	3	3	2	3
COMPLETED	2	2	3	3	2	3
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention Period
STARTED	2	2	3	3	2	3
COMPLETED	2	2	3	3	2	3
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	All participants randomized to any treatment.(Amlodipine tablet first, amlodipine ODT first, and amlodipine ODT without water first).
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.22 (7.22)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%

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 10mg Tablet With Water (Reference Product A)	Amlodipine 10 mg ODT With Water (Test Product B)	Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
Measure Participants	17	15	16
Geometric Mean (Full Range) [hr*ng/mL]	307.225	324.324	330.411

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT With Water (Test Product B)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	105.57
	Confidence Interval	(2-Sided) 90%; 98.09 to 113.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT Without Water (Test Product C)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	107.55
	Confidence Interval	(2-Sided) 90%; 99.98 to 115.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg ODT With Water (Test Product B), Amlodipine 10 mg ODT Without Water (Test Product C)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	101.88
	Confidence Interval	(2-Sided) 90%; 94.70 to 109.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC 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 10mg Tablet With Water (Reference Product A)	Amlodipine 10 mg ODT With Water (Test Product B)	Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
Measure Participants	17	15	16
Geometric Mean (Full Range) [hr*ng/mL]	275.302	285.974	287.035

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT With Water (Test Product B)
	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 ratio of geometric means
	Estimated Value	103.88
	Confidence Interval	(2-Sided) 90%; 97.27 to 110.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT Without Water (Test Product C)
	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 ratio of geometric means
	Estimated Value	104.26
	Confidence Interval	(2-Sided) 90%; 97.67 to 111.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg ODT With Water (Test Product B), Amlodipine 10 mg ODT Without Water (Test Product C)
	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 ratio of geometric means
	Estimated Value	100.37
	Confidence Interval	(2-Sided) 90%; 94.02 to 107.15
	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 10mg Tablet With Water (Reference Product A)	Amlodipine 10 mg ODT With Water (Test Product B)	Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
Measure Participants	17	15	16
Geometric Mean (Full Range) [ng/mL]	5.201	5.117	4.952

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT With Water (Test Product B)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	98.39
	Confidence Interval	(2-Sided) 90%; 91.05 to 106.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10mg Tablet With Water (Reference Product A), Amlodipine 10 mg ODT Without Water (Test Product C)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	95.22
	Confidence Interval	(2-Sided) 90%; 88.16 to 102.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Amlodipine 10 mg ODT With Water (Test Product B), Amlodipine 10 mg ODT Without Water (Test Product C)
	Comments	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.
	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 ratio of geometric means
	Estimated Value	96.77
	Confidence Interval	(2-Sided) 90%; 89.58 to 104.54
	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 10mg Tablet With Water (Reference Product A)	Amlodipine 10 mg ODT With Water (Test Product B)	Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
Measure Participants	17	15	16
Median (Full Range) [hr]	8.00	10.00	13.00

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 10mg Tablet With Water (Reference Product A)	Amlodipine 10 mg ODT With Water (Test Product B)	Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.	Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
Measure Participants	17	15	16
Mean (Standard Deviation) [hr]	44.004 (13.759)	46.698 (14.739)	49.869 (19.638)

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 10mg Tablet With Water (Reference Product A)		Amlodipine 10 mg ODT With Water (Test Product B)		Amlodipine 10 mg ODT Without Water (Test Product C)
Arm/Group Description	Treatment A (single oral dose of amlodipine 10 mg tablet with 240 ml water [Reference product A]) on Day 1 in first intervention period. Treatment B (single oral dose of amlodipine 10 mg ODT with 240 ml water [Test product B]) on Day 1 of second intervention period. Treatment C (single oral dose of amlodipine 10 mg ODT without water [Test product C]) on Day 1 of third intervention period. Participants received all treatments in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.		Test product B (single oral dose of amlodipine 10 mg ODT with 240 ml water) on Day 1 in first intervention period, followed by treatment with either Reference product A (single oral dose of amlodipine 10 mg tablet with 240 ml water) or Test product C (single oral dose of amlodipine 10 mg ODT without water) on Day 1 of second and third intervention period, respectively. Participants received treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.		Test product C without water on Day 1 in first intervention period, followed by treatment with either Reference product A or Test product B on Day 1 of second and third intervention period, respectively Participants received all treatment in the morning under fasted conditions in all the 3 periods. A washout period of 16 days was maintained between each period.
All Cause Mortality
	Amlodipine 10mg Tablet With Water (Reference Product A)		Amlodipine 10 mg ODT With Water (Test Product B)		Amlodipine 10 mg ODT Without Water (Test Product C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Amlodipine 10mg Tablet With Water (Reference Product A)		Amlodipine 10 mg ODT With Water (Test Product B)		Amlodipine 10 mg ODT Without Water (Test Product C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Amlodipine 10mg Tablet With Water (Reference Product A)		Amlodipine 10 mg ODT With Water (Test Product B)		Amlodipine 10 mg ODT Without Water (Test Product C)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/18 (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.