Evaluation Of Sperm Production With Healthy Male Volunteers Receiving Lyrica Or Placebo

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00631696
• Collaborator: (none)
• Enrollment: 222
• Locations: 13
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 17.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is being performed as a Phase IV FDA commitment study and is being powered adequately to assess changes in sperm concentration, FSH and testosterone in healthy male subjects treated with pregabalin as compared to placebo, in addition to confirming lack of effects on sperm motility.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Pregabalin; Drug: Placebo	Phase 4

Detailed Description

This is a Phase 4 FDA commitment study. The purpose of the study is to evaluate the effects of pregabalin as compared to placebo on sperm concentration in healthy male subjects

Study Design

• Study Type: Interventional
• Actual Enrollment: 222 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Other
• Official Title: Prospective Randomized Double-Blind Study Of Sperm Production In Healthy Volunteers Receiving Pregabalin Or Placebo
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Pregabalin; pregabalin 600 mg given twice a day
Placebo Comparator: 2	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a 50 Percent (%) or More Reduction in Sperm Concentration From Baseline (Bsl) to End of Study (EOS) [Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)]

   Baseline is the average of sperm concentrations from semen samples collected on or before Study Day 1. End of study is average of sperm concentrations from semen samples collected at end of washout period (Week 26) following 12 weeks of double-blind treatment. Mean sperm concentration (MSC) of a visit is average of the 2 sperm concentration samples collected at that visit. If sperm concentration was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead. Confidence intervals (CI) based on exact distribution.

Secondary Outcome Measures

1. Change From Baseline in Follicle Stimulating Hormone (FSH) to End of Study (EOS) [Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)]

   FSH minimum normal range 1.4 International units per liter (IU/L) to maximum normal range 18.1 IU/L. End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.

2. Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 26 [Baseline, Week 26 (last observation in the Week 26 window)]

   FSH minimum normal range 1.4 IU/L to maximum normal range 18.1 IU/L. Week 26 was the non-missing value within 134 to 252 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 26 analysis.

3. Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 12 [Baseline, Week 12 (last observation in the Week 12 window)]

   FSH minimum normal range 1.4 IU/L to maximum normal range 18.1 IU/L. Week 12 was the last non-missing value within 2 to 133 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 12 analysis.

4. Change From Baseline in Testosterone to End of Study (EOS) [Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)]

   End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.

5. Change From Baseline in Testosterone to Week 26 [Baseline, Week 26 (last observation in the Week 26 window)]

   Week 26 was the non-missing value within 134 to 252 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 26 analysis.

6. Change From Baseline in Testosterone to Week 12 [Baseline, Week 12 (last observation in the Week 12 window)]

   Week 12 was the last non-missing value within 2 to 133 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 12 analysis.

7. Change From Baseline in Sperm Motility to End of Study (EOS) [Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)]

   Mean sperm motility (percent motility representing grade a+b [a=sperm with progressive, straight-line motility; b=non-linear motility]) was average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.

8. Change From Baseline in Sperm Motility to Week 26 [Baseline, Week 26 (last observation in the Week 26 window)]

   Mean sperm motility (percent motility representing grade a+b) was the average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. Week 26 was average of the last 2 values within window of 134 to 252 days from Study Day 1 and at least 1 of the 2 values was non-missing. If only 1 assessment date within the stated window, Week 26 was the value of that single assessment. If all values within window were missing, the records were not to be used for Week 26 analysis.

9. Change From Baseline in Sperm Motility to Week 12 [Baseline, Week 12 (last observation in the Week 12 window)]

   Mean sperm motility (percent motility representing grade a+b) was average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. Week 12 was average of last 2 values within window of 2 to 133 days from Study Day 1 and at least 1 of the 2 values was non-missing. If there was only 1 assessment date within the stated window, then Week 12 was the value of that single assessment. If all the values within the window were missing, then the records were not to be used for Week 12 analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy 18 to 55 years old males

Exclusion Criteria:

• Screening sperm count <20 x 106/mL; screening sperm motility <50% motile (a+b) or <25% Class "a" motile or screening sperm morphology <30% normal or semen volume <1.5 mL or white blood cell count >1 x 106 /mL on any screening visit sample

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Mobile	Alabama	United States	36607
2	Pfizer Investigational Site	Phoenix	Arizona	United States	85013
3	Pfizer Investigational Site	Tarzana	California	United States	91356
4	Pfizer Investigational Site	Ocala	Florida	United States	34474
5	Pfizer Investigational Site	Madisonville	Kentucky	United States	42431
6	Pfizer Investigational Site	Shreveport	Louisiana	United States	71103
7	Pfizer Investigational Site	Shreveport	Louisiana	United States	71106
8	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48109
9	Pfizer Investigational Site	Minneapolis	Minnesota	United States	55455
10	Pfizer Investigational Site	Las Vegas	Nevada	United States	89148
11	Pfizer Investigational Site	Durham	North Carolina	United States	27713
12	Pfizer Investigational Site	Cumberland	Rhode Island	United States	02864
13	Pfizer Investigational Site	San Antonio	Texas	United States	78229

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: NCT00631696
• Other Study ID Numbers: A0081104
• First Posted: Mar 10, 2008
• Last Update Posted: Jan 26, 2021
• Last Verified: Sep 1, 2012

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Healthy males Human volunteers pregabalin or placebo sperm quality and quantity
• Additional relevant MeSH terms: Pregabalin

Study Results

Participant Flow

Recruitment Details	Study was conducted at 12 centers in the United States between February 2008 and February 2012; 903 participants were screened and 222 were assigned to study treatment.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 milligrams (mg) by mouth (PO) twice a day (BID) starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Period Title: Overall Study
STARTED	112	110
Received Study Treatment (Tx)	111	109
Ongoing at Database Release 18Oct2011	2	0
COMPLETED	75	70
NOT COMPLETED	37	40

Baseline Characteristics

Arm/Group Title	Pregabalin	Placebo	Total
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.	Total of all reporting groups
Overall Participants	111	109	220
Age, Customized (participants) [Number]
Between 18 and 44 years	100 90.1%	93 85.3%	193 87.7%
Between 45 and 64 years	11 9.9%	16 14.7%	27 12.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	111 100%	109 100%	220 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a 50 Percent (%) or More Reduction in Sperm Concentration From Baseline (Bsl) to End of Study (EOS)
Description	Baseline is the average of sperm concentrations from semen samples collected on or before Study Day 1. End of study is average of sperm concentrations from semen samples collected at end of washout period (Week 26) following 12 weeks of double-blind treatment. Mean sperm concentration (MSC) of a visit is average of the 2 sperm concentration samples collected at that visit. If sperm concentration was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead. Confidence intervals (CI) based on exact distribution.
Time Frame	Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Outcome Measure Data

Analysis Population Description

Per protocol analysis set: all randomized participants who had ≥8 weeks of study treatment, sperm concentration measurements at or after week 12 window, did not discontinue for site violations, and did not have any major protocol violations. N=number of participants with analyzable data at observation; Last observation carried forward (LOCF).

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	65	62
Number (95% Confidence Interval) [percentage of participants]	9.2 8.3%	3.2 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Study powered to show non-inferiority (NI) of pregabalin (PGB) to placebo (PBO) on the percentage of participants (N) with a ≥50% reduction in MSC from Bsl to end of washout (Week (Wk) 26, or last assessment on or after Wk 12 if Wk 26 not done). NI to be declared if upper bound of 95% CI for difference between PGB and PBO not >20%. Assuming proportion of N with 50% reduction to be 6% for both groups, sample size N=65 per group would provide >90% power to show NI of PGB to PBO.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	A non-inferiority margin of 20% was used to test the hypothesis. The null hypothesis is that the difference (PGB - PBO) in the proportion of participants with ≥50% reduction in sperm concentration is ≥20% and the alternative hypothesis is that the difference in proportion of participant with ≥50% reduction in sperm concentration is <20%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage difference
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -2.29 to 14.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	The confidence interval was based on asymptotic normal distribution.

2. Secondary Outcome

Title	Change From Baseline in Follicle Stimulating Hormone (FSH) to End of Study (EOS)
Description	FSH minimum normal range 1.4 International units per liter (IU/L) to maximum normal range 18.1 IU/L. End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.
Time Frame	Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population included all randomized participants who received at least 1 dose of study medication (either pregabalin or placebo) and were not discontinued for major violation at the site level. N=number of participants with analyzable data at observation; LOCF.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	72
Baseline	3.17 (1.624)	3.68 (1.997)
Change to EOS	0.14 (0.746)	0.22 (0.953)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3462
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.385 to 0.136
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

3. Secondary Outcome

Title	Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 26
Description	FSH minimum normal range 1.4 IU/L to maximum normal range 18.1 IU/L. Week 26 was the non-missing value within 134 to 252 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 26 analysis.
Time Frame	Baseline, Week 26 (last observation in the Week 26 window)

Outcome Measure Data

Analysis Population Description

MITT population; N=number of participants (observed cases) with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	69	60
Baseline	3.20 (1.685)	3.69 (2.050)
Change to Week 26	0.16 (0.757)	0.21 (0.949)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3652
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.420 to 0.156
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

4. Secondary Outcome

Title	Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 12
Description	FSH minimum normal range 1.4 IU/L to maximum normal range 18.1 IU/L. Week 12 was the last non-missing value within 2 to 133 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 12 analysis.
Time Frame	Baseline, Week 12 (last observation in the Week 12 window)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	72
Baseline	3.17 (1.624)	3.68 (1.997)
Change to Week 12	-0.05 (0.785)	0.08 (0.974)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1204
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.464 to 0.054
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

5. Secondary Outcome

Title	Change From Baseline in Testosterone to End of Study (EOS)
Description	End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.
Time Frame	Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation; LOCF.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	72
Baseline	518.2 (179.13)	481.8 (171.07)
Change to EOS	10.4 (170.78)	0.8 (150.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2875
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.65
	Confidence Interval	(2-Sided) 95%; -20.999 to 70.302
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

6. Secondary Outcome

Title	Change From Baseline in Testosterone to Week 26
Description	Week 26 was the non-missing value within 134 to 252 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 26 analysis.
Time Frame	Baseline, Week 26 (last observation in the Week 26 window)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	69	60
Baseline	517.9 (182.34)	474.6 (167.09)
Change to Week 26	13.8 (171.37)	2.6 (146.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1699
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.93
	Confidence Interval	(2-Sided) 95%; -14.292 to 80.158
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

7. Secondary Outcome

Title	Change From Baseline in Testosterone to Week 12
Description	Week 12 was the last non-missing value within 2 to 133 days from Study Day 1. If there were multiple observations between the stated study days (all non-missing or a combination of missing and non-missing), then the latest non-missing value was selected for analysis. If all the values within the stated window were missing, then the records were not to be used for Week 12 analysis.
Time Frame	Baseline, Week 12 (last observation in the Week 12 window)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	72
Baseline	518.2 (179.13)	481.8 (171.07)
Change to Week 12	-14.8 (169.56)	0.0 (123.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7958
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.12
	Confidence Interval	(2-Sided) 95%; -52.804 to 40.558
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

8. Secondary Outcome

Title	Change From Baseline in Sperm Motility to End of Study (EOS)
Description	Mean sperm motility (percent motility representing grade a+b [a=sperm with progressive, straight-line motility; b=non-linear motility]) was average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. End of study was the end of the washout period (Week 26) following 12 weeks of double-blind treatment. If the semen parameter was not assessed at Week 26, then the last assessment on or after Week 12 (end of treatment) was used instead.
Time Frame	Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation; LOCF.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	73
Baseline	61.9 (9.98)	61.4 (8.32)
Change to EOS	-3.2 (10.57)	-1.8 (7.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4094
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) 95%; -3.645 to 1.494
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

9. Secondary Outcome

Title	Change From Baseline in Sperm Motility to Week 26
Description	Mean sperm motility (percent motility representing grade a+b) was the average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. Week 26 was average of the last 2 values within window of 134 to 252 days from Study Day 1 and at least 1 of the 2 values was non-missing. If only 1 assessment date within the stated window, Week 26 was the value of that single assessment. If all values within window were missing, the records were not to be used for Week 26 analysis.
Time Frame	Baseline, Week 26 (last observation in the Week 26 window)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	69	60
Baseline	61.8 (10.46)	61.2 (8.71)
Change to Week 26	-2.6 (9.71)	-1.8 (6.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9064
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -2.649 to 2.352
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

10. Secondary Outcome

Title	Change From Baseline in Sperm Motility to Week 12
Description	Mean sperm motility (percent motility representing grade a+b) was average of 2 samples collected at that visit. Normal value is ≥50% motility measured within 60 minutes of collection; higher values=greater percentage of sperm with motility. Week 12 was average of last 2 values within window of 2 to 133 days from Study Day 1 and at least 1 of the 2 values was non-missing. If there was only 1 assessment date within the stated window, then Week 12 was the value of that single assessment. If all the values within the window were missing, then the records were not to be used for Week 12 analysis.
Time Frame	Baseline, Week 12 (last observation in the Week 12 window)

Outcome Measure Data

Analysis Population Description

MITT; N=number of participants with analyzable data at observation.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.	Placebo matching pregabalin treatment.
Measure Participants	79	73
Baseline	61.95 (9.976)	61.38 (8.316)
Change to Week 12	-3.94 (8.570)	-2.71 (8.186)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4666
	Comments	p-value from analysis of covariance (ANCOVA) with treatment and center as main effects and baseline value as covariate in the model.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 95%; -3.207 to 1.477
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least Squares Mean (LS Mean) and 95% CI from ANCOVA with treatment and center as main effects and baseline value as covariate in the model. LS Mean Difference calculated as (Pregabalin - Placebo).

Adverse Events

Time Frame	Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012).
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	Pregabalin		Placebo
Arm/Group Description	Pregabalin 50 mg PO BID starting dose with a 2-week titration followed by a fixed dose of 300 mg PO BID for 10 weeks, a 1 week taper at Week 12, and a 13 week washout period up to Week 26.		Placebo matching pregabalin treatment.
All Cause Mortality
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/109 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/111 (38.7%)		18/109 (16.5%)
Gastrointestinal disorders
Nausea	2/111 (1.8%)		4/109 (3.7%)
General disorders
Fatigue	5/111 (4.5%)		1/109 (0.9%)
Injury, poisoning and procedural complications
Muscle strain	4/111 (3.6%)		1/109 (0.9%)
Nervous system disorders
Dizziness	21/111 (18.9%)		1/109 (0.9%)
Headache	4/111 (3.6%)		5/109 (4.6%)
Paraesthesia	4/111 (3.6%)		1/109 (0.9%)
Somnolence	11/111 (9.9%)		5/109 (4.6%)
Psychiatric disorders
Euphoric mood	6/111 (5.4%)		1/109 (0.9%)

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.