Phase 1 Study To Test the Bioequivalence Between Two 25 mg Tablets vs. One 50 mg Tablet Under Fast/Fed Condition and Evaluate Food Effect of Desvenlafaxine Succinate Sustained Release (DVS SR)

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01190514
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Duration (Months): 2
• Patients Per Site Per Month: 20.5

Study Details

Study Description

Brief Summary

To determine the bioequivalence of 2 tablets of 25 mg sustained release (SR) formulation of DVS and 1 tablet of 50 mg SR formulation of DVS under fed and fast conditions.

To investigate the effect of high-fat meal on pharmacokinetics of desvenlafaxine after administration of 50 mg SR formulation of DVS.

Condition or Disease	Intervention/Treatment	Phase
Depression - Major Depressive Disorder	Drug: desvenlafaxine succinate sustained release; Drug: desvenlafaxine succinate sustained release; Drug: desvenlafaxine succinate sustained release; Drug: desvenlafaxine succinate sustained release	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Open-Label, Randomized, Single-Dose, 4-Treatment, 4-Period Crossover Bioequivalence Study Comparing 25 Mg and 50 Mg Formulations of DVS-233 SR and Investigate Food Effect on 50 Mg Formulations of DVS-233 SR Tablet Under Fed and Fasted Conditions
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bioequivalence and Food effect

Drug: desvenlafaxine succinate sustained release; Two tablets of 25 mg, single administration, under fed condition; Other Names: DVS-233 SR, Pristiq ; Drug: desvenlafaxine succinate sustained release; One tablet of 50 mg, single administration, under fed condition; Other Names: DVS-233 SR, Pristiq ; Drug: desvenlafaxine succinate sustained release; Two tablets of 25 mg, single administration, under fast condition; Other Names: DVS-233 SR, Pristiq ; Drug: desvenlafaxine succinate sustained release; One tablet of 50 mg, single administration, under fast condition; Other Names: DVS-233 SR, Pristiq

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

   Area under the plasma concentration versus time curve from time zero (pre-dose) to 48 hours post dose; measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL).

2. Maximum Plasma Concentration (Cmax) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

   Cmax measured as nanograms divided by milliliters (ng/mL).

Secondary Outcome Measures

1. Time to Reach Maximum Observed Plasma Concentration (Tmax) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

2. Terminal Elimination Half-life (t 1/2) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

   Terminal elimination (plasma decay) half-life is the time measured for the plasma concentration to decrease by one half.

3. Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

   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 - ∞).

4. Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast) [Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose]

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 female subjects.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bruxelles		Belgium	B-1070

Sponsors and Collaborators

• Pfizer

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
• ClinicalTrials.gov Identifier: NCT01190514
• Other Study ID Numbers: B2061035
• First Posted: Aug 27, 2010
• Last Update Posted: Jan 27, 2012
• Last Verified: Dec 1, 2011

• Keywords provided by Pfizer: DVS SR; healthy; Bioequivalence study
• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Major; Desvenlafaxine Succinate

Study Results

Participant Flow

Pre-assignment Detail	Participants randomized to an open-label treatment sequence beginning in Period 1 with 25 milligrams as 2 tablets (25 mg*2) in fed state=A; or a 50 mg tablet in fed state=B; or 25 mg*2 tablets in fasted state=C; or a 50 mg tablet in fasted state=D in a cross-over, 4-period design. Treatment groups sequenced as: ABCD, BADC, CDAB, and DCBA.

Arm/Group Title	DVS SR 25 mg*2 Fed (A) First	DVS SR 50 mg Fed (B) First	DVS SR 25 mg*2 Fasted (C) First	DVS SR 50 mg Fasted (D) First
Arm/Group Description	Desvenlafaxine sustained release (DVS SR) formulation (PF-0212375) 25 milligrams (mg) as 2 tablets (25 mg*2) on Day 1 of study period in fed state (finished a high-fat breakfast 20 minutes prior to dosing).	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state (fasted 8 hours prior to dosing).	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Period Title: First Intervention (Period 1)
STARTED	11	10	10	10
COMPLETED	10	10	10	10
NOT COMPLETED	1	0	0	0
Period Title: First Intervention (Period 1)
STARTED	10	10	10	10
COMPLETED	10	10	10	10
NOT COMPLETED	0	0	0	0
Period Title: First Intervention (Period 1)
STARTED	10	10	10	10
COMPLETED	9	10	10	10
NOT COMPLETED	1	0	0	0
Period Title: First Intervention (Period 1)
STARTED	9	10	10	10
COMPLETED	9	10	10	10
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Participants randomized to 1 of the 4 treatment sequences beginning with DVS SR 25 mg*2 Fed (A); or DVS SR 50 mg Fed (B); or DVS SR 25 mg*2 Fasted (C); or DVS SR 50 mg Fasted (D).
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.6 (10.6)
Sex: Female, Male (Count of Participants)
Female	21 51.2%
Male	20 48.8%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 to 48 Hours (AUC48)
Description	Area under the plasma concentration versus time curve from time zero (pre-dose) to 48 hours post dose; measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL).
Time Frame	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameter analysis (PK) population: all participants randomized and treated and had at least 1 of the PK parameters of primary interest in at least 1 treatment period. N=number of participants contributing to the mean.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Mean (Standard Deviation) [ng*hr/mL]	2948 (726.28)	2966 (836.52)	2632 (764.41)	2777 (893.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 25 mg*2 Fasted, DVS SR 50 mg Fasted
	Comments	DVS SR 25 mg*2 fasted (test); DVS SR 50 mg fasted (reference). Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for AUC48 fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio (%) of adjusted geometric means
	Estimated Value	95.56
	Confidence Interval	(2-Sided) 90%; 86.94 to 105.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DVS SR 25 mg*2 Fed, DVS SR 50 mg Fed
	Comments	DVS SR 25 mg*2 fed (test); DVS SR 50 mg fed (reference). Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for AUC48 fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio (%) of adjusted geometric means
	Estimated Value	101.31
	Confidence Interval	(2-Sided) 90%; 97.17 to 105.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg Fed, DVS SR 50 mg Fasted
	Comments	Food effect DVS SR 50 mg fed (test) versus DVS SR 50 mg fasted (reference). Natural log transformed AUC48: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for AUC48 fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio (%) of adjusted geometric means
	Estimated Value	108.76
	Confidence Interval	(2-Sided) 90%; 101.10 to 117.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

2. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population; N=number of participants contributing to the median.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Median (Full Range) [hours]	6.00	8.00	6.00	6.00

3. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Description	Cmax measured as nanograms divided by milliliters (ng/mL).
Time Frame	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population; N=number of participants contributing to the mean.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Mean (Standard Deviation) [ng/mL]	130.6 (29.711)	131.0 (36.308)	107.3 (26.773)	112.1 (28.510)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 25 mg*2 Fasted, DVS SR 50 mg Fasted
	Comments	DVS SR 25 mg*2 fasted (test); DVS SR 50 mg fasted (reference). Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%) of adjusted geometric means
	Estimated Value	95.10
	Confidence Interval	(2-Sided) 90%; 89.37 to 101.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DVS SR 25 mg*2 Fed, DVS SR 50 mg Fed
	Comments	DVS SR 25 mg*2 fed (test); DVS SR 50 mg fed (reference). Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (%) of adjusted geometric means
	Estimated Value	101.30
	Confidence Interval	(2-Sided) 90%; 94.66 to 108.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg Fed, DVS SR 50 mg Fasted
	Comments	Food effect DVS SR 50 mg fed (test) versus DVS SR 50 mg fasted (reference). Natural log transformed Cmax: mixed models analysis with sequence, period, treatment (formulation by food status) as fixed effects and subject within sequence as a random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Bioequivalence of the two treatments was to be concluded if the 90% CIs for the ratio of adjusted geometric means for Cmax fell wholly within (80%, 125%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio (%) of adjusted geometric means
	Estimated Value	115.54
	Confidence Interval	(2-Sided) 90%; 108.59 to 122.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference and the 90% CI for the difference were exponentiated to provide an estimate of the ratio of adjusted geometric means (test/reference).

4. Secondary Outcome

Title	Terminal Elimination Half-life (t 1/2)
Description	Terminal elimination (plasma decay) half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population; N=number of participants contributing to the median.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Mean (Standard Deviation) [hours]	10.50 (2.2478)	10.72 (2.8931)	12.71 (6.0106)	11.13 (2.9444)

5. Secondary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)
Description	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	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population; N=number of participants contributing to the mean.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Mean (Standard Deviation) [ng*hr/mL]	3171 (820.37)	3216 (973.36)	3008 (1147.6)	3052 (1059.9)

6. Secondary Outcome

Title	Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUClast)
Time Frame	Day 1 of Periods 1, 2, 3, and 4: pre-dose, 0 hour, and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population; N=number of participants contributing to the mean.

Arm/Group Title	DVS SR 25 mg*2 Fed	DVS SR 50 mg Fed	DVS SR 25 mg*2 Fasted	DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state.	DVS SR 50 mg tablet on Day 1 of study period in fed state.	DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state.	DVS SR 50 mg tablet on Day 1 of study period in fasted state.
Measure Participants	41	40	40	39
Mean (Standard Deviation) [ng*hr/mL]	2948 (726.28)	2966 (836.47)	2631 (767.89)	2778 (894.03)

Adverse Events

Time Frame	Events collected from the time of informed consent up to 28 days after last dose of study treatment.
Adverse Event Reporting Description	Same event may appear as both an AE and SAE, however, are presented as distinct events; may be categorized as SAE in 1 subject and as non-SAE in another, or 1 subject may have experienced both an SAE and non-SAE during study. Participants are counted multiple times due to the transition through the cross-over sequences.
Arm/Group Title	DVS SR 25 mg*2 Fed		DVS SR 50 mg Fed		DVS SR 25 mg*2 Fasted		DVS SR 50 mg Fasted
Arm/Group Description	DVS SR 25 mg*2 tablets on Day 1 of study period in fed state (finished a high-fat breakfast 20 minutes prior to dosing).		DVS SR 50 mg tablet on Day 1 of study period in fed state.		DVS SR 25 mg*2 tablets on Day 1 of study period in fasted state (fasted 8 hours prior to dosing).		DVS SR 50 mg tablet on Day 1 of study period in fasted state.
All Cause Mortality
	DVS SR 25 mg*2 Fed		DVS SR 50 mg Fed		DVS SR 25 mg*2 Fasted		DVS SR 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DVS SR 25 mg*2 Fed		DVS SR 50 mg Fed		DVS SR 25 mg*2 Fasted		DVS SR 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	DVS SR 25 mg*2 Fed		DVS SR 50 mg Fed		DVS SR 25 mg*2 Fasted		DVS SR 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/41 (46.3%)		19/40 (47.5%)		19/40 (47.5%)		16/39 (41%)
Eye disorders
Eyelid irritation	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/41 (0%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
Abdominal distension	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		0/39 (0%)
Diarrhoea	2/41 (4.9%)		1/40 (2.5%)		1/40 (2.5%)		1/39 (2.6%)
Dyspepsia	1/41 (2.4%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
Epigastric discomfort	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Flatulence	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		0/39 (0%)
Nausea	2/41 (4.9%)		4/40 (10%)		0/40 (0%)		0/39 (0%)
Salivary hypersecretion	1/41 (2.4%)		1/40 (2.5%)		1/40 (2.5%)		1/39 (2.6%)
Vomiting	0/41 (0%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
General disorders
Asthenia	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		0/39 (0%)
Fatigue	2/41 (4.9%)		4/40 (10%)		3/40 (7.5%)		3/39 (7.7%)
Hunger	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		2/39 (5.1%)
Vessel puncture site haematoma	1/41 (2.4%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
Vessel puncture site pain	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		1/39 (2.6%)
Infections and infestations
Bronchitis	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		0/39 (0%)
Hordeolum	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		1/39 (2.6%)
Nasopharyngitis	0/41 (0%)		0/40 (0%)		1/40 (2.5%)		1/39 (2.6%)
Oral herpes	0/41 (0%)		1/40 (2.5%)		1/40 (2.5%)		0/39 (0%)
Urinary tract infection	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		1/39 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/41 (0%)		0/40 (0%)		0/40 (0%)		2/39 (5.1%)
Musculoskeletal chest pain	2/41 (4.9%)		2/40 (5%)		1/40 (2.5%)		1/39 (2.6%)
Neck pain	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Pain in jaw	1/41 (2.4%)		1/40 (2.5%)		1/40 (2.5%)		0/39 (0%)
Nervous system disorders
Dizziness	0/41 (0%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
Head discomfort	2/41 (4.9%)		0/40 (0%)		1/40 (2.5%)		0/39 (0%)
Headache	4/41 (9.8%)		4/40 (10%)		5/40 (12.5%)		4/39 (10.3%)
Somnolence	5/41 (12.2%)		1/40 (2.5%)		4/40 (10%)		2/39 (5.1%)
Psychiatric disorders
Abnormal dreams	0/41 (0%)		1/40 (2.5%)		0/40 (0%)		0/39 (0%)
Confusional state	0/41 (0%)		0/40 (0%)		0/40 (0%)		1/39 (2.6%)
Reproductive system and breast disorders
Ejaculation delayed	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		1/39 (2.6%)
Metrorrhagia	1/41 (2.4%)		0/40 (0%)		0/40 (0%)		0/39 (0%)
Vascular disorders
Haematoma	1/41 (2.4%)		1/40 (2.5%)		1/40 (2.5%)		1/39 (2.6%)
Hot flush	0/41 (0%)		1/40 (2.5%)		2/40 (5%)		0/39 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.