Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01004614
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 48.7

Study Details

Study Description

Brief Summary

This study is being conducted to determine if 5 mg amlodipine 3rd Orally-Disintegrating (OD) tablet (new formulation) and 5 mg amlodipine 2nd OD tablet (commercial formulation) are bioequivalent.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Amlodipine; Drug: Amlodipine; Drug: Amlodipine; Drug: Amlodipine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open, Randomized, Parallel-Cohort, 2-Periods, Crossover, Single Dose Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet In Healthy Male Subjects
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 24 subjects (12 subjects per sequence) will receive treatment A) one 5 mg amlodipine 3rd OD tablet (test) with water and treatment B) one 5 mg amlodipine 2nd OD tablet (reference) with water.	Drug: Amlodipine; 3rd OD 5 mg tablet single oral dose administered with water; Drug: Amlodipine; 2nd OD 5 mg tablet single oral dose administered with water
Active Comparator: Cohort 2 24 subjects (12 subjects per sequence) will receive treatment C) one 5 mg amlodipine 3rd OD tablet (test) without water, and treatment D) one 5 mg amlodipine 2nd OD tablet (reference) without water	Drug: Amlodipine; 3rd OD 5 mg tablet single oral dose administered without water; Drug: Amlodipine; 2nd OD 5 mg tablet single oral dose administered without water

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-Time Curve From Zero Time Until the Last Sampling Time (AUCt) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

   Area under the concentration-time curve from zero time until the last sampling time

2. Maximum Observed Plasma Concentration (Cmax) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

Secondary Outcome Measures

1. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast), Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

   AUC last = Area under the concentration versus time curve from zero time until the last measurable concentration is calculated using the trapezoidal rule. AUCinf = AUClast + (Ct / kel), where Ct is the estimated concentration at the last measurable concentration.

2. Apparent Terminal Elimination Phase Rate Constant (Kel) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

   Estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile.

3. Apparent Terminal Elimination Half-Life (T-half) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

   Terminal phase half-life calculated as ln(2) / kel

4. Mean Residence Time (MRT) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

   MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method.

5. Time to Reach Maximum Observed Plasma Concentration (Tmax) [prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy;

• Body Mass Index (BMI) of 18 to 28 kg/m2;

• total body weight within the range of 50 to 100 kg

Exclusion Criteria:

• History of regular alcohol consumption exceeding 14 drinks/week

• Use of tobacco- or nicotine-containing products in excess of the equivalent of 10 cigarettes per day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Minato-ku	Tokyo	Japan

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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: NCT01004614
• Other Study ID Numbers: A0531088
• First Posted: Oct 30, 2009
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Amlodipine

Study Results

Participant Flow

Recruitment Details	Participants were screened at one center in Japan.
Pre-assignment Detail	This study consisted of 2 cohorts (I and II). The design of each cohort was an open-label, randomized, 2-periods, crossover, single-dose study in healthy adult male subjects. A washout period of at least 14 days was taken between each administration in Periods 1 and 2.

Arm/Group Title	3rd OD Tablet With Water, Then 2nd OD Tablet With Water	2nd OD Tablet With Water, Then 3rd OD Tablet With Water	3rd OD Tablet Without Water, Then 2nd OD Tablet Without Water	2nd OD Tablet Without Water, Then 3rd OD Tablet Without Water
Arm/Group Description	One amlodipine third generation orally disintegrating (OD) 5 mg tablet (test) taken with water during the first intervention period, then one amlodipine second generation OD 5 mg tablet (reference) taken with water during second intervention period. A washout of 14 days was retained between periods.	One amlodipine second generation OD 5 mg tablet (reference) taken with water during the first intervention period, then one amlodipine third generation OD 5 mg tablet (test) taken with water during the second intervention period. A washout of 14 days was retained between periods.	One amlodipine third generation OD 5 mg tablet (test) taken without water during the first intervention period, then one amlodipine second generation OD 5 mg tablet (reference) taken without water during the second intervention period. A washout of 14 days was retained between periods.	One amlodipine second generation OD 5mg tablet (reference) taken without water during the first intervention period, then one amlodipine third generation OD 5 mg tablet (test) taken without water during the second intervention period. A washout of 14 days was retained between periods.
Period Title: First Intervention
STARTED	12	12	12	12
COMPLETED	12	12	12	12
NOT COMPLETED	0	0	0	0
Period Title: First Intervention
STARTED	12	12	12	12
COMPLETED	12	11	12	12
NOT COMPLETED	0	1	0	0
Period Title: First Intervention
STARTED	12	11	12	12
COMPLETED	12	11	12	12
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	3rd OD Tablet With Water, Then 2nd OD Tablet With Water	2nd OD Tablet With Water, Then 3rd OD Tablet With Water	3rd OD Tablet Without Water, Then 2nd OD Tablet Without Water	2nd OD Tablet Without Water, Then 3rd OD Tablet Without Water	Total
Arm/Group Description	One amlodipine third generation orally disintegrating (OD) 5 mg tablet (test) taken with water during the first intervention period, then one amlodipine second generation OD 5 mg tablet (reference) taken with water during the second intervention period. A washout of 14 days was retained between periods.	One amlodipine second generation OD 5mg tablet (reference) taken with water during the first intervention period, then one amlodipine third generation OD 5 mg tablet (test) taken with water during the second intervention period. A washout of 14 days was retained between periods.	One amlodipine third generation OD 5 mg tablet (test) taken without water during the first intervention period, then one amlodipine second generation OD 5 mg tablet (reference) taken without water during the second intervention period. A washout of 14 days was retained between periods.	One amlodipine second generation OD 5mg tablet (reference) taken without water during the first intervention period, then one amlodipine third generation OD 5 mg tablet (test) taken without water during the second intervention period. A washout of 14 days was retained between periods.	Total of all reporting groups
Overall Participants	12	12	12	12	48
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.8 (10.7)	32.4 (11.1)	37.3 (9.0)	37.8 (12.1)	33.1 (10.7)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	12 100%	12 100%	12 100%	12 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-Time Curve From Zero Time Until the Last Sampling Time (AUCt)
Description	Area under the concentration-time curve from zero time until the last sampling time
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Mean (Standard Deviation) [ng*h/mL]	126.36 (33.16)	129.48 (39.93)	122.33 (32.59)	119.75 (28.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: 3rd OD Tablet (Test) With Water, Cohort I: 2nd OD Tablet (Reference) With Water, Cohort II: 3rd OD Tablet (Test) Without Water, Cohort II: 2nd OD Tablet (Reference) Without Water
	Comments	Natural log transformed AUCt was analyzed using a mixed effects model with sequence, period and formulation as fixed effects and subject within sequence as a random effect. Adjusted mean difference (test - reference) and 90% CI was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean and 90% CI for the ratio. Alternative hypothesis of bioequivalence: (H1: θL <=µT - µR <=θU); null hypothesis of inequivalence: (Ho: µT - µR <θL or µT - µR >θU).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence of the two formulations was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCt and Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratios of adjusted geometric mean
	Estimated Value	98.61
	Confidence Interval	(2-Sided) 90%; 93.09 to 104.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter estimate = ratio (%) (test/reference) of adjusted geometric means.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort I: 3rd OD Tablet (Test) With Water, Cohort I: 2nd OD Tablet (Reference) With Water, Cohort II: 3rd OD Tablet (Test) Without Water, Cohort II: 2nd OD Tablet (Reference) Without Water
	Comments	Natural log transformed AUCt was analyzed using a mixed effects model with sequence, period and formulation as fixed effects and subject within sequence as a random effect. Adjusted mean difference (test - reference) and 90% CI was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean and 90% CI for the ratio. Alternative hypothesis of bioequivalence: (H1: θL <=µT - µR <=θU); null hypothesis of inequivalence: (Ho: µT - µR <θL or µT - µR >θU).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence of the two formulations was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCt and Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratios of adjusted geometric mean
	Estimated Value	101.29
	Confidence Interval	(2-Sided) 90%; 97.28 to 105.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Parameter estimate = ratio (%) (test/reference) of adjusted geometric means.

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Mean (Standard Deviation) [ng/mL]	2.70 (0.513)	2.74 (0.650)	2.48 (0.470)	2.45 (0.409)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort I: 3rd OD Tablet (Test) With Water, Cohort I: 2nd OD Tablet (Reference) With Water, Cohort II: 3rd OD Tablet (Test) Without Water, Cohort II: 2nd OD Tablet (Reference) Without Water
	Comments	Natural log transformed Cmax was analyzed using a mixed effects model with sequence, period and formulation as fixed effects and subject within sequence as a random effect. Adjusted mean difference (test - reference) and 90% CI was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean and 90% CI for the ratio. Alternative hypothesis of bioequivalence: (H1: θL <=µT - µR <=θU); null hypothesis of inequivalence: (Ho: µT - µR <θL or µT - µR >θU).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence of the two formulations was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCt and Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratios of adjusted geometric mean
	Estimated Value	99.30
	Confidence Interval	(2-Sided) 90%; 92.28 to 106.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort I: 3rd OD Tablet (Test) With Water, Cohort I: 2nd OD Tablet (Reference) With Water, Cohort II: 3rd OD Tablet (Test) Without Water, Cohort II: 2nd OD Tablet (Reference) Without Water
	Comments	Natural log transformed Cmax was analyzed using a mixed effects model with sequence, period and formulation as fixed effects and subject within sequence as a random effect. Adjusted mean difference (test - reference) and 90% CI was obtained from the model and exponentiated to provide estimates of the ratio of adjusted geometric mean and 90% CI for the ratio. Alternative hypothesis of bioequivalence: (H1: θL <=µT - µR <=θU); null hypothesis of inequivalence: (Ho: µT - µR <θL or µT - µR >θU).
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Bioequivalence of the two formulations was concluded if the 90% confidence intervals for the ratio of adjusted geometric means for both AUCt and Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratios of adjusted geometric mean
	Estimated Value	100.84
	Confidence Interval	(2-Sided) 90%; 95.93 to 106.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast), Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf)
Description	AUC last = Area under the concentration versus time curve from zero time until the last measurable concentration is calculated using the trapezoidal rule. AUCinf = AUClast + (Ct / kel), where Ct is the estimated concentration at the last measurable concentration.
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
AUClast	124.14 (33.96)	127.36 (40.91)	121.05 (33.76)	118.27 (29.43)
AUCinf	142.87 (43.20)	145.22 (49.19)	140.41 (42.18)	138.14 (34.10)

4. Secondary Outcome

Title	Apparent Terminal Elimination Phase Rate Constant (Kel)
Description	Estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile.
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Mean (Standard Deviation) [L/h]	0.0174 (0.0031)	0.0179 (0.0035)	0.0162 (0.0041)	0.0156 (0.0031)

5. Secondary Outcome

Title	Apparent Terminal Elimination Half-Life (T-half)
Description	Terminal phase half-life calculated as ln(2) / kel
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Mean (Standard Deviation) [hour]	41.45 (9.76)	40.27 (8.48)	45.04 (10.16)	46.20 (8.85)

6. Secondary Outcome

Title	Mean Residence Time (MRT)
Description	MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method.
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Mean (Standard Deviation) [hour]	61.29 (13.55)	59.77 (11.99)	66.18 (14.10)	67.33 (11.90)

7. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame	prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

Arm/Group Title	Cohort I: 3rd OD Tablet (Test) With Water	Cohort I: 2nd OD Tablet (Reference) With Water	Cohort II: 3rd OD Tablet (Test) Without Water	Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose	Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose	Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose	Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
Measure Participants	23	23	24	24
Median (Full Range) [hour]	8	8	8	8

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	Cohort I: 3rd OD Tablet (Test) With Water		Cohort I: 2nd OD Tablet (Reference) With Water		Cohort II: 3rd OD Tablet (Test) Without Water		Cohort II: 2nd OD Tablet (Reference) Without Water
Arm/Group Description	Cohort I: One 5 mg amlodipine 3rd OD tablet (test) taken with water as a single oral dose		Cohort I: One 5 mg amlodipine 2nd OD tablet (reference) taken with water as a single oral dose		Cohort II: One 5 mg amlodipine 3rd OD tablet (test) taken without water as a single oral dose		Cohort II: One 5 mg amlodipine 2nd OD tablet (reference) taken without water as a single oral dose
All Cause Mortality
	Cohort I: 3rd OD Tablet (Test) With Water		Cohort I: 2nd OD Tablet (Reference) With Water		Cohort II: 3rd OD Tablet (Test) Without Water		Cohort II: 2nd OD Tablet (Reference) Without Water
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort I: 3rd OD Tablet (Test) With Water		Cohort I: 2nd OD Tablet (Reference) With Water		Cohort II: 3rd OD Tablet (Test) Without Water		Cohort II: 2nd OD Tablet (Reference) Without Water
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Cohort I: 3rd OD Tablet (Test) With Water		Cohort I: 2nd OD Tablet (Reference) With Water		Cohort II: 3rd OD Tablet (Test) Without Water		Cohort II: 2nd OD Tablet (Reference) Without Water
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/23 (30.4%)		6/24 (25%)		2/24 (8.3%)		3/24 (12.5%)
Gastrointestinal disorders
Abdominal discomfort	1/23 (4.3%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Diarrhoea	0/23 (0%)		0/24 (0%)		1/24 (4.2%)		0/24 (0%)
Stomatitis	0/23 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Toothache	1/23 (4.3%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Infections and infestations
Pharingitis	1/23 (4.3%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Investigations
Blood bilirubin increased	0/23 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Blood uric acid increased	0/23 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/23 (4.3%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Musculoskeletal stiffness	1/23 (4.3%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Nervous system disorders
Headache	2/23 (8.7%)		1/24 (4.2%)		0/24 (0%)		1/24 (4.2%)
Somnolence	0/23 (0%)		0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal disconfort	1/23 (4.3%)		1/24 (4.2%)		0/24 (0%)		0/24 (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.