Trial Outcomes & Findings for Pregabalin in Treating Women With Hot Flashes (NCT NCT00702949)

NCT ID: NCT00702949

Last Updated: 2016-08-01

Results Overview

Hot flash activity will be analyzed in a number of ways. For the primary analysis, the numerical change-from-baseline to hot flash score after week 6 of treatment will be compared between the highest dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

207 participants

Primary outcome timeframe

Baseline, after week 6 of treatment

Results posted on

2016-08-01

Participant Flow

Total of 207 patients were enrolled on this trial between 06/20/2008, and 07/21/2008.

There were 16 cancels (6 in Arm I, 3 in Arm II and 7 in Arm III).

Participant milestones

Participant milestones
Measure	Pregabalin75 Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	Pregabalin150 Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Overall Study STARTED	63	66	62
Overall Study Evaluable for Primary Endpoint	56	56	51
Overall Study COMPLETED	58	57	54
Overall Study NOT COMPLETED	5	9	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin75 Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	Pregabalin150 Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Overall Study Refusal	3	2	2
Overall Study Adverse Event	1	6	3
Overall Study Other Medical Reason/unknown	1	1	3

Baseline Characteristics

Pregabalin in Treating Women With Hot Flashes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin75 n=63 Participants Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	Pregabalin150 n=66 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=62 Participants Patients receive oral placebo twice daily for 6 weeks.	Total n=191 Participants Total of all reporting groups
Age, Continuous	64.5 years STANDARD_DEVIATION 10.6 • n=5 Participants	60.6 years STANDARD_DEVIATION 9.5 • n=7 Participants	56.6 years STANDARD_DEVIATION 6.4 • n=5 Participants	60.3 years STANDARD_DEVIATION 8.9 • n=4 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	66 Participants n=7 Participants	62 Participants n=5 Participants	191 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	63 participants n=5 Participants	66 participants n=7 Participants	62 participants n=5 Participants	191 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, after week 6 of treatment

Population: Arm II: 66 EPs, 56 are EFP and 10 are not (2 off-study by refusal, 6 AE, 1 unknown reason and 1 NODATA). Arm III: 62 EPs, 51 are EFP and 11 are not (2 off-study by refusal, 3 AE, 3 NODATA and 3 due to other reasons).

Hot flash activity will be analyzed in a number of ways. For the primary analysis, the numerical change-from-baseline to hot flash score after week 6 of treatment will be compared between the highest dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-9.6 units on a scale Interval -12.9 to -7.6	-6.1 units on a scale Interval -7.9 to -2.9	—

PRIMARY outcome

Timeframe: Baseline, after week 6 of treatment

Population: Arm II: 66 EPs, 56 are EFP and 10 are not (2 off-study by refusal, 6 AE, 1 unknown reason and 1 NODATA). Arm III: 62 EPs, 51 are EFP and 11 are not (2 off-study by refusal, 3 AE, 3 NODATA and 3 due to other reasons).

Hot flash activity will be analyzed in a number of ways. For the primary analysis, the percent change-from-baseline to hot flash score after week 6 of treatment will be compared between the highest dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-71.0 percent change Interval -78.2 to -60.6	-50.1 percent change Interval -64.5 to -28.3	—

SECONDARY outcome

Timeframe: Baseline, after week 6 of treatment

The analysis of daily average hot flash frequency will follow as specified for the primary analysis. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=56 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.
Numerical Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-4.6 Hot flashes per day Interval -5.6 to -3.9	-4.9 Hot flashes per day Interval -6.1 to -4.0	-2.9 Hot flashes per day Interval -3.6 to -1.4

SECONDARY outcome

Timeframe: Baseline, after week 6 of treatment

The analysis of daily average hot flash frequency will follow as specified for the primary analysis. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=56 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.
Percent Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-58.5 percent change Interval -74.6 to -48.8	-61.1 percent change Interval -72.3 to -48.3	-36.3 percent change Interval -51.6 to -20.3

SECONDARY outcome

Timeframe: Baseline, after week 6 of treatment

Population: Arm I: 63 EPs, 56 are EFP and 7 are not (3 off-study by refusal, 1 AE, 2 NODATA and 1 due to other medical reasons). Arm III: 62 EPs, 51 are EFP and 11 are not (2 off-study by refusal, 3 AE, 3 NODATA and 3 due to other reasons).

Hot flash activity will be analyzed in a number of ways. For the this analysis, the numerical change-from-baseline to hot flash score after week 6 of treatment will be compared between the lower dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Comparison of 75 mg of Pregabalin vs Placebo, Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-9.7 units on a scale Interval -12.1 to -7.3	-6.1 units on a scale Interval -7.9 to -2.9	—

SECONDARY outcome

Timeframe: Baseline, after week 6 of treatment

Population: Arm I: 63 EPs, 56 are EFP and 7 are not (3 off-study by refusal, 1 AE, 2 NODATA and 1 due to other medical reasons). Arm III: 62 EPs, 51 are EFP and 11 are not (2 off-study by refusal, 3 AE, 3 NODATA and 3 due to other reasons).

Hot flash activity will be analyzed in a number of ways. For the this analysis, the percent change-from-baseline to hot flash score after week 6 of treatment will be compared between the lower dose treatment arm and the placebo arm. A hot flash score is computed for each patient by assigning points (1=mild, 2=moderate, 3=severe, 4=very severe) to each hot flash based on patient-reported severity, adding the points for each day, and averaging across each week of the study. Abbreviations for the analysis population description: Eligible patients (EPs). Evaluable for primary (EFP). Off-study for adverse event (AE). Do not have 6 weeks of data (NODATA).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=56 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=51 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo Patients receive oral placebo twice daily for 6 weeks.
Comparison of 75 mg of Pregabalin vs Placebo. Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	-64.9 percent change Interval -83.6 to -57.8	-50.1 percent change Interval -64.5 to -28.3	—

SECONDARY outcome

Timeframe: Baseline, 6 weeks during treatment.

A descriptive report of the toxicities experienced by participants will be measured with a Symptom Experience Diary. Participants will complete this questionnaire weekly. This patient diary contains several questions related to potential side effects and side benefits of pregabalin measured on a numeric analogue scale (based on 0-10 scale with 10 being worst toxicity, providing numbers representing the worst median changes from baseline minus Maximum (Week 1-6) Symptom Experience Diary Distributions).

Outcome measures

Outcome measures
Measure	Pregabalin150 n=63 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=66 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo n=62 Participants Patients receive oral placebo twice daily for 6 weeks.
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about concentration	1.0 units on a scale Interval -3.0 to 8.0	1.0 units on a scale Interval -3.0 to 9.0	0.0 units on a scale Interval -4.0 to 9.0
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about weight gain	1.0 units on a scale Interval -2.0 to 10.0	2.0 units on a scale Interval -2.0 to 10.0	1.0 units on a scale Interval -9.0 to 10.0
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about sleepiness	1.0 units on a scale Interval -6.0 to 8.0	2.0 units on a scale Interval -4.0 to 9.0	1.0 units on a scale Interval -5.0 to 6.0
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about dizziness	1.0 units on a scale Interval -2.0 to 7.0	2.0 units on a scale Interval -2.0 to 9.0	0 units on a scale Interval -4.0 to 8.0
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about coordination	0.0 units on a scale Interval -3.0 to 6.0	1.0 units on a scale Interval -3.0 to 9.0	0.0 units on a scale Interval -3.0 to 8.0
Toxicity Data for the Individual Study Arms From the Symptom Experience Diary . Concern about blurred/double vision	0.0 units on a scale Interval -3.0 to 7.0	1.0 units on a scale Interval -1.0 to 7.0	0.0 units on a scale Interval 0.0 to 7.0

SECONDARY outcome

Timeframe: Baseline, after week 6 of treatment.

Endpoints for this analysis will be median change from baseline to after week 6 of treatment. Hot Flash Related Daily Interference Scale is used to evaluate the specific impact of the study treatment on the effect hot flashes have on various life activities such as work, social, leisure and relationships. Responses to the questionnaire are recorded on a 0 to 10 scale. Lower scores are better.

Outcome measures

Outcome measures
Measure	Pregabalin150 n=63 Participants Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=66 Participants Patients receive oral placebo twice daily for 6 weeks.	Placebo n=62 Participants Patients receive oral placebo twice daily for 6 weeks.
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Work	-1.0 units on a scale Interval -6.0 to 4.0	-1.5 units on a scale Interval -10.0 to 5.0	-1 units on a scale Interval -8.0 to 2.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Social Activities	-1 units on a scale Interval -7.0 to 4.0	-1.5 units on a scale Interval -8.0 to 4.0	0 units on a scale Interval -7.0 to 7.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Leisure Activities	-1 units on a scale Interval -8.0 to 4.0	-1 units on a scale Interval -8.0 to 4.0	0 units on a scale Interval -6.0 to 5.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Sleep	-2 units on a scale Interval -10.0 to 3.0	-3 units on a scale Interval -10.0 to 3.0	-1 units on a scale Interval -9.0 to 3.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Mood	-1 units on a scale Interval -7.0 to 4.0	-1 units on a scale Interval -8.0 to 6.0	0 units on a scale Interval -7.0 to 7.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Concentration	-1 units on a scale Interval -7.0 to 6.0	-1 units on a scale Interval -7.0 to 4.0	-1 units on a scale Interval -8.0 to 5.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Relations	-1 units on a scale Interval -6.0 to 6.0	0 units on a scale Interval -8.0 to 2.0	0 units on a scale Interval -7.0 to 3.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Sexuality	0 units on a scale Interval -5.0 to 4.0	0 units on a scale Interval -9.0 to 2.0	0 units on a scale Interval -9.0 to 7.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Enjoy Life	-1 units on a scale Interval -10.0 to 5.0	-2 units on a scale Interval -10.0 to 2.0	-1 units on a scale Interval -8.0 to 3.0
Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks of Treatment Overall QOL	-1.5 units on a scale Interval -10.0 to 5.0	-1.5 units on a scale Interval -9.0 to 2.0	0 units on a scale Interval -8.0 to 2.0

Adverse Events

Pregabalin75

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

Pregabalin150

Serious events: 0 serious events

Other events: 56 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Pregabalin75 n=63 participants at risk Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	Pregabalin150 n=66 participants at risk Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Placebo n=62 participants at risk Patients receive oral placebo twice daily for 6 weeks.
Ear and labyrinth disorders Hearing loss	0.00% 0/63	1.5% 1/66 • Number of events 1	0.00% 0/62
Eye disorders Diplopia	4.8% 3/63 • Number of events 3	4.5% 3/66 • Number of events 4	0.00% 0/62
Eye disorders Vision blurred	15.9% 10/63 • Number of events 19	25.8% 17/66 • Number of events 25	14.5% 9/62 • Number of events 14
Gastrointestinal disorders Constipation	30.2% 19/63 • Number of events 38	42.4% 28/66 • Number of events 55	27.4% 17/62 • Number of events 33
Gastrointestinal disorders Diarrhea	1.6% 1/63 • Number of events 1	0.00% 0/66	0.00% 0/62
General disorders Edema limbs	20.6% 13/63 • Number of events 22	36.4% 24/66 • Number of events 40	25.8% 16/62 • Number of events 35
General disorders Fatigue	4.8% 3/63 • Number of events 5	4.5% 3/66 • Number of events 5	1.6% 1/62 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/63	1.5% 1/66 • Number of events 1	0.00% 0/62
Nervous system disorders Cognitive disturbance	17.5% 11/63 • Number of events 20	37.9% 25/66 • Number of events 41	17.7% 11/62 • Number of events 26
Nervous system disorders Depressed level of consciousness	0.00% 0/63	1.5% 1/66 • Number of events 1	0.00% 0/62
Nervous system disorders Dizziness	41.3% 26/63 • Number of events 48	53.0% 35/66 • Number of events 60	22.6% 14/62 • Number of events 28
Nervous system disorders Headache	0.00% 0/63	0.00% 0/66	1.6% 1/62 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/63	0.00% 0/66	1.6% 1/62 • Number of events 1
Nervous system disorders Speech disorder	1.6% 1/63 • Number of events 2	0.00% 0/66	0.00% 0/62
Nervous system disorders Syncope	1.6% 1/63 • Number of events 1	0.00% 0/66	1.6% 1/62 • Number of events 1
Psychiatric disorders Agitation	1.6% 1/63 • Number of events 2	0.00% 0/66	0.00% 0/62
Psychiatric disorders Anxiety	0.00% 0/63	1.5% 1/66 • Number of events 1	0.00% 0/62
Psychiatric disorders Insomnia	1.6% 1/63 • Number of events 1	3.0% 2/66 • Number of events 2	0.00% 0/62
Psychiatric disorders Orgasm abnormal	1.6% 1/63 • Number of events 1	0.00% 0/66	0.00% 0/62
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/63	0.00% 0/66	1.6% 1/62 • Number of events 1
Vascular disorders Hot flashes	1.6% 1/63 • Number of events 1	1.5% 1/66 • Number of events 1	1.6% 1/62 • Number of events 1
Vascular disorders Hypertension	0.00% 0/63	0.00% 0/66	1.6% 1/62 • Number of events 1

Additional Information

Charles Loprinzi, M.D.

Mayo Clinic

Phone: 507/284-1623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place