Trial Outcomes & Findings for Evaluation Of Sperm Production With Healthy Male Volunteers Receiving Lyrica Or Placebo (NCT NCT00631696)

NCT ID: NCT00631696

Last Updated: 2021-01-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 222 participants
• Primary outcome timeframe: Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)
• Results posted on: 2021-01-26

Participant Flow

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.

Participant milestones

Measure	Pregabalin 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 Placebo matching pregabalin treatment.
Overall Study STARTED	112	110
Overall Study Received Study Treatment (Tx)	111	109
Overall Study Ongoing at Database Release 18Oct2011	2	0
Overall Study COMPLETED	75	70
Overall Study NOT COMPLETED	37	40

Reasons for withdrawal

Measure	Pregabalin 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 Placebo matching pregabalin treatment.
Overall Study Entered, not randomized to treatment	1	1
Overall Study Discontinued after database release date	1	0
Overall Study Follow up after database release date	1	0
Overall Study Lost to Follow-up	7	10
Overall Study Withdrawal by Subject	2	9
Overall Study Other	8	8
Overall Study Protocol Violation	9	9
Overall Study Study terminated by sponsor	3	3
Overall Study Adverse Event	5	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Pregabalin n=111 Participants 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 n=109 Participants Placebo matching pregabalin treatment.	Total n=220 Participants Total of all reporting groups
Age, Customized Between 18 and 44 years	100 participants n=5 Participants	93 participants n=7 Participants	193 participants n=5 Participants
Age, Customized Between 45 and 64 years	11 participants n=5 Participants	16 participants n=7 Participants	27 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	111 Participants n=5 Participants	109 Participants n=7 Participants	220 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Population: 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).

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.

Outcome measures

Measure	Pregabalin n=65 Participants 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 n=62 Participants Placebo matching pregabalin treatment.
Percentage of Participants With a 50 Percent (%) or More Reduction in Sperm Concentration From Baseline (Bsl) to End of Study (EOS)	9.2 percentage of participants Interval 3.46 to 19.02	3.2 percentage of participants Interval 0.39 to 11.17

SECONDARY outcome

Timeframe: Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

Population: 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.

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=72 Participants Placebo matching pregabalin treatment.
Change From Baseline in Follicle Stimulating Hormone (FSH) to End of Study (EOS) Baseline	3.17 IU/L Standard Deviation 1.624	3.68 IU/L Standard Deviation 1.997
Change From Baseline in Follicle Stimulating Hormone (FSH) to End of Study (EOS) Change to EOS	0.14 IU/L Standard Deviation 0.746	0.22 IU/L Standard Deviation 0.953

SECONDARY outcome

Timeframe: Baseline, Week 26 (last observation in the Week 26 window)

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

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.

Outcome measures

Measure	Pregabalin n=69 Participants 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 n=60 Participants Placebo matching pregabalin treatment.
Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 26 Change to Week 26	0.16 IU/L Standard Deviation 0.757	0.21 IU/L Standard Deviation 0.949
Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 26 Baseline	3.20 IU/L Standard Deviation 1.685	3.69 IU/L Standard Deviation 2.050

SECONDARY outcome

Timeframe: Baseline, Week 12 (last observation in the Week 12 window)

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

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=72 Participants Placebo matching pregabalin treatment.
Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 12 Baseline	3.17 IU/L Standard Deviation 1.624	3.68 IU/L Standard Deviation 1.997
Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 12 Change to Week 12	-0.05 IU/L Standard Deviation 0.785	0.08 IU/L Standard Deviation 0.974

SECONDARY outcome

Timeframe: Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

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

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=72 Participants Placebo matching pregabalin treatment.
Change From Baseline in Testosterone to End of Study (EOS) Baseline	518.2 nanograms per deciliter (ng/dL) Standard Deviation 179.13	481.8 nanograms per deciliter (ng/dL) Standard Deviation 171.07
Change From Baseline in Testosterone to End of Study (EOS) Change to EOS	10.4 nanograms per deciliter (ng/dL) Standard Deviation 170.78	0.8 nanograms per deciliter (ng/dL) Standard Deviation 150.64

SECONDARY outcome

Timeframe: Baseline, Week 26 (last observation in the Week 26 window)

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

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.

Outcome measures

Measure	Pregabalin n=69 Participants 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 n=60 Participants Placebo matching pregabalin treatment.
Change From Baseline in Testosterone to Week 26 Change to Week 26	13.8 ng/dL Standard Deviation 171.37	2.6 ng/dL Standard Deviation 146.80
Change From Baseline in Testosterone to Week 26 Baseline	517.9 ng/dL Standard Deviation 182.34	474.6 ng/dL Standard Deviation 167.09

SECONDARY outcome

Timeframe: Baseline, Week 12 (last observation in the Week 12 window)

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

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=72 Participants Placebo matching pregabalin treatment.
Change From Baseline in Testosterone to Week 12 Baseline	518.2 ng/dL Standard Deviation 179.13	481.8 ng/dL Standard Deviation 171.07
Change From Baseline in Testosterone to Week 12 Change to Week 12	-14.8 ng/dL Standard Deviation 169.56	0.0 ng/dL Standard Deviation 123.61

SECONDARY outcome

Timeframe: Baseline, End of Study (last observation at Week 26 or last assessment on or after Week 12 if no data at Week 26)

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

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=73 Participants Placebo matching pregabalin treatment.
Change From Baseline in Sperm Motility to End of Study (EOS) Baseline	61.9 percent motility Standard Deviation 9.98	61.4 percent motility Standard Deviation 8.32
Change From Baseline in Sperm Motility to End of Study (EOS) Change to EOS	-3.2 percent motility Standard Deviation 10.57	-1.8 percent motility Standard Deviation 7.49

SECONDARY outcome

Timeframe: Baseline, Week 26 (last observation in the Week 26 window)

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

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.

Outcome measures

Measure	Pregabalin n=69 Participants 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 n=60 Participants Placebo matching pregabalin treatment.
Change From Baseline in Sperm Motility to Week 26 Baseline	61.8 percent motility Standard Deviation 10.46	61.2 percent motility Standard Deviation 8.71
Change From Baseline in Sperm Motility to Week 26 Change to Week 26	-2.6 percent motility Standard Deviation 9.71	-1.8 percent motility Standard Deviation 6.52

SECONDARY outcome

Timeframe: Baseline, Week 12 (last observation in the Week 12 window)

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

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.

Outcome measures

Measure	Pregabalin n=79 Participants 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 n=73 Participants Placebo matching pregabalin treatment.
Change From Baseline in Sperm Motility to Week 12 Baseline	61.95 percent motility Standard Deviation 9.976	61.38 percent motility Standard Deviation 8.316
Change From Baseline in Sperm Motility to Week 12 Change to Week 12	-3.94 percent motility Standard Deviation 8.570	-2.71 percent motility Standard Deviation 8.186

Adverse Events

Pregabalin

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pregabalin n=111 participants at risk 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 n=109 participants at risk Placebo matching pregabalin treatment.
Gastrointestinal disorders Nausea	1.8% 2/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	3.7% 4/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
General disorders Fatigue	4.5% 5/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	0.92% 1/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Injury, poisoning and procedural complications Muscle strain	3.6% 4/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	0.92% 1/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Nervous system disorders Dizziness	18.9% 21/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	0.92% 1/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Nervous system disorders Headache	3.6% 4/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	4.6% 5/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Nervous system disorders Paraesthesia	3.6% 4/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	0.92% 1/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Nervous system disorders Somnolence	9.9% 11/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	4.6% 5/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.
Psychiatric disorders Euphoric mood	5.4% 6/111 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.	0.92% 1/109 • Treatment emergent Adverse Events are collected from the time of first dose of study treatment through last subject last visit (06 February 2012). 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER