Pregabalin in Treating Women With Hot Flashes | NCT00702949

ID	Type	Description	Link
NCI-2012-02716	Registry Identifier	CTRP (Clinical Trials Reporting System)
CDR0000598191	Registry Identifier	PDQ (Physician Data Query)

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

To evaluate the efficacy of 150 mg of pregabalin versus placebo on hot flash scores in women with a history of breast cancer or women who do not wish to take estrogen therapy for fear of increased risk of breast cancer.
To evaluate the side effect profile of different doses of pregabalin in these patients.
To evaluate the effect of 150 mg of pregabalin versus placebo on the secondary outcome of interference of activities from hot flashes in these patients.
To evaluate the efficacy and side effect profile of 75 mg of pregabalin versus placebo in these patients.

OUTLINE: Patients are stratified according to age (18-49 years vs ≥ 50 years); selective estrogen-receptor modulator (i.e., tamoxifen or raloxifene) or aromatase inhibitor use (yes vs no); duration of hot flashes (< 9 months vs ≥ 9 months); and frequency of hot flashes per 24-hour period (4-9 vs ≥ 10). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
Arm II: Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
Arm III: Patients receive oral placebo twice daily for 6 weeks. Treatment in all arms continues in the absence of unacceptable toxicity.

Patients complete Hot Flash Diaries at baseline and once daily during treatment and the Symptom Experience Diary at baseline and once weekly during treatment. Patients also complete the Profile of Mood States and the Hot Flash Related Daily Interference Scale questionnaires at baseline and after completion of study treatment.

Label	Type	Description	Intervention Names
Pregabalin75	Experimental	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	Drug: pregabalin
Pregabalin150	Experimental	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	Drug: pregabalin
Placebo	Placebo Comparator	Patients receive oral placebo twice daily for 6 weeks.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
pregabalin	Drug	Given orally	Pregabalin150 Pregabalin75

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	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).	Baseline, after week 6 of treatment
Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	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).	Baseline, after week 6 of treatment

Secondary Outcomes

Measure	Description	Time Frame
Numerical Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).	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).

Eligibility Module

Name	Affiliation	Role
Charles Loprinzi, MD	Mayo Clinic	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259-5499	United States
Aurora Presbyterian Hospital

PubMed Identifier	Type	Citation	Retractions
	Result	Loprinzi CL, Qin R, Stella PJ, et al.: Pregabalin for hot flashes in women: NCCTG trial N07C1. [Abstract] J Clin Oncol 27 (Suppl 15): A-9513, 2009.

ID	Title	Description
FG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
FG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Numerical Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).

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).

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).

Posted

Median

95% Confidence Interval

units on a scale

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG001	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Units	Counts
Participants	OG00056 OG00151

Title

Denominators

Categories

Title	Measurements
	OG000-9.6(-12.9 to -7.6) OG001-6.1(-7.9 to -2.9)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Comparing the median numerical change from baseline on hot flash score for Pregabalin 150 Mg with the Placebo.	t-test, 2 sided		0.007						2-Sided							No	Superiority or Other

Secondary

Numerical Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).

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).

Posted

Median

95% Confidence Interval

Hot flashes per day

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Hot Flash Frequency at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).

Posted

Median

95% Confidence Interval

percent change

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Units	Counts
Participants

Secondary

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).

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).

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).

Posted

Median

95% Confidence Interval

units on a scale

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Secondary

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).

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).

Posted

Median

95% Confidence Interval

percent change

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Secondary

Toxicity Data for the Individual Study Arms From the Symptom Experience Diary .

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).

Posted

Median

Full Range

units on a scale

Baseline, 6 weeks during treatment.

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Units	Counts

Primary

Percent Change From Baseline in Hot Flash Score at Treatment Week 6 (Positive Numbers to Represent Increases and Negative Numbers to Represent Decreases).

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).

Posted

Median

95% Confidence Interval

percent change

Baseline, after week 6 of treatment

ID	Title	Description
OG000	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG001	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Secondary

Mood and Hot Flash-related Daily Interference on Activities After 6 Weeks 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.

Posted

Median

Full Range

units on a scale

Baseline, after week 6 of treatment.

ID	Title	Description
OG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
OG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
OG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hearing loss	Ear and labyrinth disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0011 events1 affected66 at risk EG0020 events0 affected62 at risk
Diplopia	Eye disorders	MedDRA 10	Systematic Assessment	EG0003 events3 affected63 at risk EG0014 events3 affected66 at risk EG0020 events0 affected62 at risk
Vision blurred	Eye disorders	MedDRA 10	Systematic Assessment	EG00019 events10 affected63 at risk EG00125 events17 affected66 at risk EG00214 events9 affected62 at risk
Constipation	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG00038 events19 affected63 at risk EG00155 events28 affected66 at risk EG00233 events17 affected62 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected63 at risk EG0010 events0 affected66 at risk EG0020 events0 affected62 at risk
Edema limbs	General disorders	MedDRA 10	Systematic Assessment	EG00022 events13 affected63 at risk EG00140 events24 affected66 at risk EG00235 events16 affected62 at risk
Fatigue	General disorders	MedDRA 10	Systematic Assessment	EG0005 events3 affected63 at risk EG0015 events3 affected66 at risk EG0021 events1 affected62 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0011 events1 affected66 at risk EG0020 events0 affected62 at risk
Cognitive disturbance	Nervous system disorders	MedDRA 10	Systematic Assessment	EG00020 events11 affected63 at risk EG00141 events25 affected66 at risk EG00226 events11 affected62 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0011 events1 affected66 at risk EG0020 events0 affected62 at risk
Dizziness	Nervous system disorders	MedDRA 10	Systematic Assessment	EG00048 events26 affected63 at risk EG00160 events35 affected66 at risk EG00228 events14 affected62 at risk
Headache	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0010 events0 affected66 at risk EG0021 events1 affected62 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0010 events0 affected66 at risk EG0021 events1 affected62 at risk
Speech disorder	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0002 events1 affected63 at risk EG0010 events0 affected66 at risk EG0020 events0 affected62 at risk
Syncope	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected63 at risk EG0010 events0 affected66 at risk EG0021 events1 affected62 at risk
Agitation	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0002 events1 affected63 at risk EG0010 events0 affected66 at risk EG0020 events0 affected62 at risk
Anxiety	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0011 events1 affected66 at risk EG0020 events0 affected62 at risk
Insomnia	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected63 at risk EG0012 events2 affected66 at risk EG0020 events0 affected62 at risk
Orgasm abnormal	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected63 at risk EG0010 events0 affected66 at risk EG0020 events0 affected62 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0010 events0 affected66 at risk EG0021 events1 affected62 at risk
Hot flashes	Vascular disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected63 at risk EG0011 events1 affected66 at risk EG0021 events1 affected62 at risk
Hypertension	Vascular disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected63 at risk EG0010 events0 affected66 at risk EG0021 events1 affected62 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.
BG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.
BG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pregabalin75	Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.	63	42	63
EG001	Pregabalin150	Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.	66	56	66
EG002	Placebo	Patients receive oral placebo twice daily for 6 weeks.	62	37	62