Hot Flashes
Conditions
Keywords
Hot Flashes, Hot Flushes, Postmenopausal symptoms, Vasomotor symptoms
Brief summary
Depomed's Gabapentin Extended Release is an investigational, extended release formulation of gabapentin that is being studied for the treatment of hot flashes in postmenopausal women
Detailed description
The primary study objective is to assess the efficacy of G-ER dosed in either of the following regimens: G-ER 1200mg daily (single evening dose) G-ER 1800mg daily (dosed asymmetrically; 600mg AM/1200mg 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.
Interventions
G-ER 1200 mg daily dosage given as two 600-mg tablets.
G-ER 1800 mg daily dosage given as one 600-mg tablet in the morning and two 600-mg tablets in the evening.
DRUGPlacebo
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).
Sponsors
Depomed
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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 effects 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | At baseline and 4 weeks of treatment | Mean change from baseline in average daily number of moderate or severe hot flashes at stable dose week (SDW) 4 of treatment relative to placebo; last observation carried forward (LOCF) analysis |
| Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | At baseline and 12 weeks of treatment | Mean change from baseline in average daily number of moderate or severe hot flashes at stable dose week (SDW) 12 of treatment relative to placebo; last observation carried forward (LOCF) analysis |
| Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | At baseline and 4 weeks of treatment | Mean change from baseline in average daily severity score of moderate or severe hot flashes at stable dose week (SDW) 4 of treatment relative to placebo; last observation carried forward (LOCF) analysis. Severity of hot flashes is scored on a scale of 1 to 3 where 1=mild, 2=moderate, 3=severe. |
| Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | At baseline and 12 weeks of treatment | Mean change from baseline in average daily severity score of moderate or severe hot flashes at stable dose week (SDW) 12 of treatment relative to placebo; last observation carried forward (LOCF) analysis. Severity of hot flashes is scored on a scale of 1 to 3 where 1=mild, 2=moderate, 3=severe. |
Countries
United States
Participant flow
Pre-assignment details
A total of 565 patients were randomly assigned to treatment: 190 in G-ER 1800 mg group, 192 in G-ER 1200 mg group, and 183 in placebo group. Of these 565 patients, 559 patients (190 in G-ER 1800 mg group, 186 in 1200 mg group, and 183 in placebo group) received study treatment and were included in intent to treat (ITT) and safety populations.
Participants by arm
| Arm | Count |
|---|---|
| G-ER 1200 mg Gabapentin extended-release (G-ER) 1200 mg | 186 |
| G-ER 1800 mg Gabapentin extended-release (G-ER) 1800 mg | 190 |
| Sugar Pill Placebo 1200 mg or 1800 mg | 183 |
| Total | 559 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 21 | 8 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 14 |
| Overall Study | Last dose date unknown | 3 | 3 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 3 |
| Overall Study | Missing data | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 1 | 1 |
| Overall Study | Reasons not specified | 4 | 4 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 8 |
Baseline characteristics
| Characteristic | G-ER 1200 mg | G-ER 1800 mg | Sugar Pill | Total |
|---|---|---|---|---|
| Age Continuous | 53.1 years STANDARD_DEVIATION 7 | 53.6 years STANDARD_DEVIATION 6.1 | 52.9 years STANDARD_DEVIATION 6 | 53.2 years STANDARD_DEVIATION 6.4 |
| Age, Customized <65 years | 175 participants | 181 participants | 177 participants | 533 participants |
| Age, Customized >=65 years | 11 participants | 9 participants | 6 participants | 26 participants |
| Frequency of hot flashes Mild | 1.1 Hot flashes STANDARD_DEVIATION 2 | 1.0 Hot flashes STANDARD_DEVIATION 2 | 1.7 Hot flashes STANDARD_DEVIATION 2.9 | 1.2 Hot flashes STANDARD_DEVIATION 2.3 |
| Frequency of hot flashes Moderate | 6.1 Hot flashes STANDARD_DEVIATION 5.8 | 5.4 Hot flashes STANDARD_DEVIATION 4 | 6.2 Hot flashes STANDARD_DEVIATION 5.1 | 5.9 Hot flashes STANDARD_DEVIATION 5 |
| Frequency of hot flashes Severe | 6.7 Hot flashes STANDARD_DEVIATION 5.1 | 6.9 Hot flashes STANDARD_DEVIATION 5.5 | 6.6 Hot flashes STANDARD_DEVIATION 4.9 | 6.8 Hot flashes STANDARD_DEVIATION 5.2 |
| Sex: Female, Male Female | 186 Participants | 190 Participants | 183 Participants | 559 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 186 | 83 / 190 | 29 / 183 |
| serious Total, serious adverse events | 2 / 186 | 2 / 190 | 2 / 183 |
Outcome results
Primary
Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 12 Weeks of Treatment
Mean change from baseline in average daily number of moderate or severe hot flashes at stable dose week (SDW) 12 of treatment relative to placebo; last observation carried forward (LOCF) analysis
Time frame: At baseline and 12 weeks of treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1200 mg | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -7.7 Hot flashes |
| G-ER 1800 mg | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -7.3 Hot flashes |
| Sugar Pill | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -6.2 Hot flashes |
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate or severe hot flashes at SDW 12p-value: 0.002497.5% CI: [-2.72, -0.41]ANCOVA
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate or severe hot flashes at SDW 12p-value: 0.028197.5% CI: [-2.26, 0.02]ANCOVA
Primary
Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 4 Weeks of Treatment
Mean change from baseline in average daily number of moderate or severe hot flashes at stable dose week (SDW) 4 of treatment relative to placebo; last observation carried forward (LOCF) analysis
Time frame: At baseline and 4 weeks of treatment
Population: Intention to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1200 mg | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -7.0 Hot flashes |
| G-ER 1800 mg | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -6.9 Hot flashes |
| Sugar Pill | Change From Baseline in Average Daily Frequency of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -5.4 Hot flashes |
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate or severe hot flashes at SDW 4p-value: 0.002497.5% CI: [-2.8, -0.42]ANCOVA
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate or severe hot flashes at SDW 4p-value: 0.00497.5% CI: [-2.69, -0.33]ANCOVA
Primary
Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 12 Weeks of Treatment
Mean change from baseline in average daily severity score of moderate or severe hot flashes at stable dose week (SDW) 12 of treatment relative to placebo; last observation carried forward (LOCF) analysis. Severity of hot flashes is scored on a scale of 1 to 3 where 1=mild, 2=moderate, 3=severe.
Time frame: At baseline and 12 weeks of treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1200 mg | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -0.8 Units on a scale |
| G-ER 1800 mg | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -0.8 Units on a scale |
| Sugar Pill | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 12 Weeks of Treatment | -0.5 Units on a scale |
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate or severe hot flashes at SDW 12p-value: 0.02897.5% CI: [-0.43, 0]ANCOVA
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate or severe hot flashes at SDW 12p-value: 0.002697.5% CI: [-0.51, -0.07]ANCOVA
Primary
Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 4 Weeks of Treatment
Mean change from baseline in average daily severity score of moderate or severe hot flashes at stable dose week (SDW) 4 of treatment relative to placebo; last observation carried forward (LOCF) analysis. Severity of hot flashes is scored on a scale of 1 to 3 where 1=mild, 2=moderate, 3=severe.
Time frame: At baseline and 4 weeks of treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1200 mg | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -0.5 Units on a scale |
| G-ER 1800 mg | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -0.6 Units on a scale |
| Sugar Pill | Change From Baseline in Average Daily Severity Score of Moderate or Severe Hot Flashes After 4 Weeks of Treatment | -0.4 Units on a scale |
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate or severe hot flashes at SDW 4p-value: 0.060897.5% CI: [-0.32, -0.03]ANCOVA
Comparison: Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate or severe hot flashes at SDW 4p-value: 0.000397.5% CI: [-0.45, -0.11]ANCOVA