Study of Gabapentin Extended Release (G-ER) in the Treatment of Vasomotor (Hot Flashes/Hot Flushes) Symptoms in Postmenopausal Women

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety and Efficacy of Gabapentin Extended Release (G-ER) Tablets in the Treatment of Vasomotor Symptoms in Postmenopausal Women

Depomed's Gabapentin Extended Release (G-ER) is an investigational, extended release formulation of gabapentin that is being studied for the treatment of hot flashes in postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Hot Flashes
• Intervention / Treatment: Drug: Gabapentin Extended-Release (G-ER) 1200 mg; Drug: Gabapentin Extended-Release (G-ER) 1800 mg; Drug: Placebo

Detailed Description

The primary study objective is to assess the efficacy of G-ER dosed in either of the following regimens:

• G-ER 1200 mg daily (single evening dose)
• G-ER 1800 mg daily (dosed asymmetrically; 600 mg in AM/1200 mg in PM) compared to placebo in reducing the average daily frequency and severity score of moderate to severe hot flashes in postmenopausal women after 4 weeks and 12 weeks of treatment with a stable dose, compared with the baseline week.

• Study Type: Interventional
• Enrollment (Actual): 541
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Montgomery, Alabama, United States
  • Arizona
    • Tempe, Arizona, United States
    • Tucson, Arizona, United States
  • California
    • Berkely, California, United States
    • La Mesa, California, United States
    • San Diego, California, United States
    • Santa Rosa, California, United States
  • Colorado
    • Denver, Colorado, United States
    • Lakewood, Colorado, United States
  • Connecticut
    • Waterbury, Connecticut, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Clearwater, Florida, United States
    • Jacksonville, Florida, United States
    • New Port Richey, Florida, United States
    • Orlando, Florida, United States
    • St. Petersburg, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Sandy Springs, Georgia, United States
    • Savannah, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kentucky
    • Madisonville, Kentucky, United States
  • Massachusetts
    • Fall River, Massachusetts, United States
  • Minnesota
    • Edina, Minnesota, United States
  • Missouri
    • St. Louis, Missouri, United States
  • Montana
    • Billings, Montana, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • Moorestown, New Jersey, United States
  • North Carolina
    • Raleigh, North Carolina, United States
    • Wilmington, North Carolina, United States
  • North Dakota
    • Fargo, North Dakota, United States
  • Ohio
    • Columbus, Ohio, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
    • West Reading, Pennsylvania, United States
  • South Carolina
    • Columbia, South Carolina, United States
    • Hilton Head Island, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Washington
    • Bellevue, Washington, United States
    • Renton, Washington, United States
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Postmenopausal women aged 18 to 70 years experiencing ≥7 moderate to severe hot flashes per day (or ≥50 per week) accompanied by sweating during previous 30 days or longer.
2. Had amenorrhea for ≥12 months, amenorrhea for 6 to 12 months with serum follicle-stimulating hormone (FSH) levels >40 mIU/mL, or was ≥6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
3. Willing to discontinue the following: vaginal hormonal products; transdermal or oral estrogen or estrogen/progestin combination; intrauterine progestin; progestin implants; injectable estrogen; topical progesterone cream.
4. Had to have daily average of ≥7 moderate to severe hot flashes and had to complete ≥4 days of diary entries during baseline week to be randomized.
5. If treated with antidepressants, could not have had any changes in drug doses during past month.

Other Inclusions apply.

Exclusion Criteria:

1. Patient treated with a gonadotrophin releasing hormone agonist, anti-estrogens, or aromatase inhibitors within 2 months prior to study entry.
2. Patient treated with estrogen pellets or progestin injectable drugs within 6 months prior to study entry.
3. Patient experience only nighttime hot flashes or worked night shifts on a regular basis.
4. Patient was concurrently treated with gabapentin for other indications. If patient was using gabapentin for treatment of hot flashes, she could be screened after a 7-day washout period provided hot flashes returned.
5. Patient had previously experienced dose-limiting adverse events that prevented titration of gabapentin to an effective dose.
6. Patient had a hypersensitivity to gabapentin.
7. Patient was in an immunocompromised state.
8. Patient had a malignancy other than basal cell carcinoma within 2 years prior to study entry.
9. Patient had gastric reduction surgery, severe chronic diarrhea, chronic constipation, uncontrolled irritable bowel syndrome, uncontrolled inflammatory bowel disease, or unexplained weight loss.
10. Patient had clinically significant abnormal chemistry or hematology results, or calculated glomerular filtration rate <60 mL/min.
11. Patient had history of substance abuse within year prior to study entry.
12. Patient was concurrently taking morphine.
13. Patient had history of chronic hepatitis B or C, hepatitis within 3 months prior to study entry, or history of human immunodeficiency virus.

Other Exclusions apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-ER 1200 mg; Gabapentin extended-release (G-ER) 1200 mg	Drug: Gabapentin Extended-Release (G-ER) 1200 mg; G-ER 1200 mg daily dosage given as two 600-mg tablets.; Other Names: Gabapentin
Experimental: G-ER 1800 mg; Gabapentin extended-release (G-ER) 1800 mg	Drug: Gabapentin Extended-Release (G-ER) 1800 mg; G-ER 1800 mg daily dosage given as one 600-mg tablet in the morning and two 600-mg tablets in the evening.; Other Names: Gabapentin
Placebo Comparator: Sugar Pill; Placebo 1200 mg or 1800 mg	Drug: Placebo; Matching placebo dosages of 1200 mg daily (two 600-mg tablets) and 1800 mg daily (one 600-mg tablet in the morning and two 600-mg tablets in the evening).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Daily Frequency of Hot Flashes After 4 Weeks of Treatment With Daily Doses of G-ER 1200 mg or G-ER 1800 mg Compared to Placebo	Change from baseline in average daily frequency of moderate to severe hot flashes after 4 weeks of treatment with stable daily doses of G-ER 1200 mg or G-ER 1800 mg compared with placebo, using last observation carried forward (LOCF) method of imputation for missing data in intent-to-treat (ITT) population.	From baseline to 4 weeks
Change From Baseline in Average Daily Frequency of Hot Flashes After 12 Weeks of Treatment With Daily Doses of G-ER 1200 mg or G-ER 1800 mg Compared to Placebo	Change from baseline in average daily frequency of moderate to severe hot flashes after 12 weeks of treatment with stable daily doses of G-ER 1200 mg or G-ER 1800 mg compared with placebo, using last observation carried forward (LOCF) method of imputation for missing data in intent-to-treat (ITT) population.	Form baseline to 12 weeks
Change From Baseline in Average Daily Severity Score of Hot Flashes After 4 Weeks of Treatment With Daily Doses of G-ER 1200 mg or G-ER 1800 mg Compared to Placebo	Change from baseline in average daily severity score of moderate to severe hot flashes after 4 weeks of treatment with stable daily doses of G-ER 1200 mg or G-ER 1800 mg compared with placebo, using last observation carried forward (LOCF) method of imputation for missing data in intent-to-treat (ITT) population. Severity score is on a 3-point scale where 1=Mild, 2=Moderate, and 3=Severe.	From baseline to 4 weeks
Change From Baseline in Average Daily Severity Score of Hot Flashes After 12 Weeks of Treatment With Daily Doses of G-ER 1200 mg or G-ER 1800 mg Compared to Placebo	Change from baseline in average daily severity score of moderate to severe hot flashes after 12 weeks of treatment with stable daily doses of G-ER 1200 mg or G-ER 1800 mg compared with placebo, using last observation carried forward (LOCF) method of imputation for missing data in intent-to-treat (ITT) population. Severity score is on a 3-point scale were 1=Mild, 2=Moderate, and 3=Severe.	From baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Depomed

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Estimate): March 7, 2012
• Last Update Submitted That Met QC Criteria: February 3, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Hot flashes; Hot flushes; Postmenopausal symptoms; Vasomotor symptoms
• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: BREEZE 1; 81-0058