Hot Flashes
Conditions
Keywords
Hot Flushes, Vasomotor Symptoms, Menopausal Hot Flashes
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/Hot Flushes in postmenopausal women
Detailed description
The primary study objective is to assess the efficacy of G-ER dosed at 1800mg daily (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 at weeks 4 & 12 of the efficacy treatment period, compared with baseline.
Interventions
DRUGGabapentin Extended Release
Gabapentin ER 1800mg daily
DRUGPlacebo
Sugar pill
Sponsors
Depomed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Generally healthy, postmenopausal women who seek treatment for hot flashes * Patients using hormone replacement therapy(HRT) must be willing to discontinue treatment * Patients must be experiencing moderate to severe hot flashes * Patients must be able to sign the informed consent * Patients must be able to enter simple commands and complete questionnaires on the frequency and severity of their hot flashes using an electronic diary Other inclusions apply.
Exclusion criteria
* Patients with hypersensitivity to Gabapentin * Patients with severe chronic diarrhea, chronic constipation, uncontrolled irritable bowel syndrome (IBS) or unexplained weight loss * Patients treated with estrogen pellets or injectable progestin drug therapy within 6 months. * Patients currently treated with Gabapentin or Pregabalin for any indication, including vasomotor symptoms Other exclusions apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline, Week 4, and Week 12 | G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline. |
| G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline, Week 4, and Week 12 | G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Week 12 and Week 24 | Proportion of patients who were categorized as very much or much improved for PGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved. |
| Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Week 12 and Week 24 | Proportion of patients who were categorized as very much or much improved in CGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved. |
| Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes | Baseline, Week 12, and Week 24 | — |
| Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes | Baseline, Week 12, and Week 24 | — |
| G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | Baseline, Week 24 | G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 24 of the efficacy treatment period compared with Baseline. |
| Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Baseline, Week 4, Week 12, and Week 24 | Insomnia Severity Index (ISI) scored on 4-point Likert-scales ('0' not at all - '4' extremely) for 7 sub-categories. Final score is sum of each sub-category generating a total sleep quality score (0-28). Minimum value = 0, maximum value = 28 (Lower scores indicate better outcome (ie, less severity)). |
| Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline, Week 4, Week 12, and Week 24 | 4 sub-categories each scored individually: Minimum value = 1, maximum value = 8. Overall summary score was mean of the 4 sub-category scores (minimum = 1 and maximum = 8). Lower scores indicate better outcome (ie, less severity) |
| Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Week 4, Week 12, Week 24/Early Termination, Week 28 | Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects were classified as 0=no suicidal ideation or 1=suicidal ideation. Outcome Measure is number of participants with or without suicidal ideation. Higher counts without suicidal ideation = better outcome. |
| Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Baseline, Week 4, Week 12, and Week 24 | Sleep Interference Score Range: Minimum value = 0, maximum value = 10 Lower scores indicate better outcome (ie, less interference) |
| G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | Baseline, Week 24 | G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 24 of the efficacy treatment period compared with Baseline. |
Countries
United States
Participant flow
Pre-assignment details
A total of 600 subjects were randomly assigned to treatment: 302 in G-ER 1800 mg group and 298 in placebo group. Of these 600 subjects, 595 subjects (300 in G-ER 1800 mg group and 295 in placebo group) received study treatment and were included in the safety population, and 593 subjects were included in the intent-to-treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| G-ER 1800 mg Gabapentin extended-release (G-ER) 1800 mg | 299 |
| Sugar Pill Placebo 1800 mg | 294 |
| Total | 593 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 49 | 35 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 12 | 15 |
| Overall Study | Lost to Follow-up | 10 | 6 |
| Overall Study | Protocol Violation | 7 | 13 |
| Overall Study | Reasons not specified | 4 | 6 |
| Overall Study | Withdrawal by Subject | 12 | 28 |
Baseline characteristics
| Characteristic | G-ER 1800 mg | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 6.1 | 54.0 years STANDARD_DEVIATION 6 | 54.0 years STANDARD_DEVIATION 6.1 |
| Age, Customized < 65 years | 280 participants | 282 participants | 562 participants |
| Age, Customized >=65 years | 19 participants | 12 participants | 31 participants |
| Frequency of hot flashes Mild | 1.5 hot flashes STANDARD_DEVIATION 2.8 | 1.5 hot flashes STANDARD_DEVIATION 3.3 | 1.5 hot flashes STANDARD_DEVIATION 3.1 |
| Frequency of hot flashes Moderate | 6.4 hot flashes STANDARD_DEVIATION 5.3 | 6.1 hot flashes STANDARD_DEVIATION 4.9 | 6.3 hot flashes STANDARD_DEVIATION 5.1 |
| Frequency of hot flashes Severe | 7.1 hot flashes STANDARD_DEVIATION 10.6 | 6.5 hot flashes STANDARD_DEVIATION 5.4 | 6.8 hot flashes STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Black | 74 participants | 82 participants | 156 participants |
| Race/Ethnicity, Customized Hispanic | 9 participants | 9 participants | 18 participants |
| Race/Ethnicity, Customized Other | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized White | 215 participants | 197 participants | 412 participants |
| Sex: Female, Male Female | 299 Participants | 294 Participants | 593 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 102 / 300 | 53 / 295 |
| serious Total, serious adverse events | 4 / 300 | 7 / 295 |
Outcome results
Primary
G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline.
G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline.
Time frame: Baseline, Week 4, and Week 12
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Frequency at Week 4 | -6.72 hot flashes |
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Frequency at Week 12 | -7.64 hot flashes |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Frequency at Week 4 | -5.01 hot flashes |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Frequency at Week 12 | -6.50 hot flashes |
Comparison: Baseline LOCF Average Daily Frequency at Week 4:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate to severe hot flashes at Week 4.p-value: 0.000395% CI: [-2.31, -1.09]Based on Van Eltereen
Comparison: Baseline LOCF Average Daily Frequency at Week 12:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily number of moderate to severe hot flashes at Week 12.p-value: 0.195% CI: [-1.8, -0.48]Based on Van Elteren
Primary
G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline.
G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline.
Time frame: Baseline, Week 4, and Week 12
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Severity at Week 4 | -0.42 scores on a scale |
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Severity at Week 12 | -0.65 scores on a scale |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Severity at Week 4 | -0.22 scores on a scale |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline. | Baseline LOCF Average Daily Severity at Week 12 | -0.46 scores on a scale |
Comparison: Baseline LOCF Average Daily Severity Score at Week 4:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate to severe hot flashes at Week 4.p-value: <0.000195% CI: [-0.31, -0.1]Based on Van Elteren
Comparison: Baseline LOCF Average Daily Severity Score at Week 12:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in average daily severity score of moderate to severe hot flashes at Week 12.p-value: 0.000495% CI: [-0.33, -0.04]Based on Van Elteren
Secondary
Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score.
Sleep Interference Score Range: Minimum value = 0, maximum value = 10 Lower scores indicate better outcome (ie, less interference)
Time frame: Baseline, Week 4, Week 12, and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| G-ER 1800 mg | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 12: LOCF daily rating | -3.09 units on a scale |
| G-ER 1800 mg | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 4: LOCF daily rating | -2.67 units on a scale |
| G-ER 1800 mg | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 24: LOCF daily rating | -3.15 units on a scale |
| Sugar Pill | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 4: LOCF daily rating | -1.31 units on a scale |
| Sugar Pill | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 12: LOCF daily rating | -2.17 units on a scale |
| Sugar Pill | Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score. | Change from Baseline to Week 24: LOCF daily rating | -2.20 units on a scale |
Comparison: Change from Baseline to Week 4: LOCF daily sleep interference rating.p-value: <0.000195% CI: [-1.75, -0.97]ANCOVA
Comparison: Change from Baseline to Week 12: LOCF daily sleep interference rating.p-value: <0.000195% CI: [-1.36, -0.47]ANCOVA
Comparison: Change from Baseline to Week 24: LOCF daily sleep interference rating.p-value: <0.000195% CI: [-1.42, -0.49]ANCOVA
Secondary
Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period.
4 sub-categories each scored individually: Minimum value = 1, maximum value = 8. Overall summary score was mean of the 4 sub-category scores (minimum = 1 and maximum = 8). Lower scores indicate better outcome (ie, less severity)
Time frame: Baseline, Week 4, Week 12, and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| G-ER 1800 mg | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 4 | -0.91 scores on a scale |
| G-ER 1800 mg | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 12 | -1.01 scores on a scale |
| G-ER 1800 mg | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 24 | -1.01 scores on a scale |
| Sugar Pill | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 4 | -0.71 scores on a scale |
| Sugar Pill | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 12 | -0.87 scores on a scale |
| Sugar Pill | Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period. | Baseline LOCF MENQOL score at Week 24 | -0.96 scores on a scale |
Comparison: MENQOL score at Week 4p-value: 0.013795% CI: [-0.37, -0.04]ANCOVA
Comparison: MENQOL score at Week 12p-value: 0.087295% CI: [-0.31, 0.02]ANCOVA
Comparison: MENQOL score at Week 24p-value: 0.560795% CI: [-0.23, 0.13]ANCOVA
Secondary
Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period.
Insomnia Severity Index (ISI) scored on 4-point Likert-scales ('0' not at all - '4' extremely) for 7 sub-categories. Final score is sum of each sub-category generating a total sleep quality score (0-28). Minimum value = 0, maximum value = 28 (Lower scores indicate better outcome (ie, less severity)).
Time frame: Baseline, Week 4, Week 12, and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| G-ER 1800 mg | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 4: LOCF ISI rating | -6.47 scores on a scale |
| G-ER 1800 mg | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 12: LOCF ISI rating | -7.02 scores on a scale |
| G-ER 1800 mg | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 24: LOCF ISI rating | -6.71 scores on a scale |
| Sugar Pill | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 4: LOCF ISI rating | -4.13 scores on a scale |
| Sugar Pill | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 12: LOCF ISI rating | -5.17 scores on a scale |
| Sugar Pill | Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period. | Change from Baseline to Week 24: LOCF ISI rating | -4.95 scores on a scale |
Comparison: Change from Baseline to Week 4: LOCF daily insomnia severity index (ISI) rating.p-value: <0.000195% CI: [-3.67, -1.56]ANCOVA
Comparison: Change from Baseline to Week 12: LOCF daily insomnia severity index (ISI) rating.p-value: 0.000795% CI: [-2.92, -0.78]ANCOVA
Comparison: Change from Baseline to Week 24: LOCF daily insomnia severity index (ISI) rating.p-value: 0.001495% CI: [-2.84, -0.69]ANCOVA
Secondary
Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period.
Proportion of patients who were categorized as very much or much improved in CGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved.
Time frame: Week 12 and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| G-ER 1800 mg | Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 12 | 173 Participants |
| G-ER 1800 mg | Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 24 | 159 Participants |
| Sugar Pill | Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 12 | 122 Participants |
| Sugar Pill | Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 24 | 124 Participants |
Comparison: Proportion of patients who were categorized as very much or much improved in CGIC at Week 12.~Null Hypotheses: no treatment differences, relative to placebo in the proportion of patients who were categorized as very much or much improved in the CGIC score at week 12.p-value: <0.000195% CI: [8.4, 24.3]2-sample Z test
Comparison: Week 24p-value: 0.00795% CI: [3, 19]2-sample Z test
Secondary
G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline.
G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 24 of the efficacy treatment period compared with Baseline.
Time frame: Baseline, Week 24
Population: Completer Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | -8.99 hot flashes |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | -7.91 hot flashes |
Comparison: Baseline LOCF Average Daily Frequency at Week 24:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in observed average daily number of moderate to severe hot flashes at Week 24.p-value: 0.15195% CI: [-1.98, -0.19]Based on Van Elteren
Secondary
G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline.
G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 24 of the efficacy treatment period compared with Baseline.
Time frame: Baseline, Week 24
Population: Completer Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| G-ER 1800 mg | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | -0.86 scores on a scale |
| Sugar Pill | G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline. | -0.64 scores on a scale |
Comparison: Baseline LOCF Average Daily Severity Score at Week 24:~Null hypothesis: no treatment differences relative to placebo in mean change from baseline in observed average daily severity score of moderate to severe hot flashes at Week 24.p-value: 0.000495% CI: [-0.44, 0]Van Elteren
Secondary
Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period.
Proportion of patients who were categorized as very much or much improved for PGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved.
Time frame: Week 12 and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| G-ER 1800 mg | Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 12 | 173 Participants |
| G-ER 1800 mg | Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 24 | 156 Participants |
| Sugar Pill | Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 12 | 130 Participants |
| Sugar Pill | Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period. | Baseline LOCF Proportion at Week 24 | 114 Participants |
Comparison: Proportion of patients who were categorized as very much or much improved in PGIC at Week 12.~Null Hypotheses: no treatment differences, relative to placebo in the proportion of patients who were categorized as very much or much improved in the PGIC score at week 12..p-value: 0.000895% CI: [5.7, 21.6]2-sample Z test
Comparison: Proportion of patients who were categorized as very much or much improved in PGIC at Week 24.p-value: 0.000995% CI: [5.5, 21.3]2-sample Z test
Secondary
Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes
Time frame: Baseline, Week 12, and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| G-ER 1800 mg | Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes | Baseline LOCF Proportion at Week 12 | 125 Participants |
| G-ER 1800 mg | Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes | Baseline LOCF Proportion at Week 24 | 146 Participants |
| Sugar Pill | Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes | Baseline LOCF Proportion at Week 12 | 101 Participants |
| Sugar Pill | Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes | Baseline LOCF Proportion at Week 24 | 122 Participants |
Comparison: Week 12p-value: 0.060995% CI: [-0.3, 15.2]two-sample Z test
Comparison: Week 24p-value: 0.07295% CI: [-0.7, 15.3]two-sample Z test
Secondary
Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes
Time frame: Baseline, Week 12, and Week 24
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| G-ER 1800 mg | Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes | Baseline LOCF Average Daily Score at Week 12 | 48 Participants |
| G-ER 1800 mg | Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes | Baseline LOCF Average Daily Score at Week 24 | 62 Participants |
| Sugar Pill | Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes | Baseline LOCF Average Daily Score at Week 12 | 36 Participants |
| Sugar Pill | Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes | Baseline LOCF Average Daily Score at Week 24 | 48 Participants |
Comparison: Week 12p-value: 0.182595% CI: [-1.8, 9.4]two-sample Z test
Comparison: Week 24p-value: 0.166295% CI: [-1.8, 10.7]two-sample Z test
Secondary
Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS).
Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects were classified as 0=no suicidal ideation or 1=suicidal ideation. Outcome Measure is number of participants with or without suicidal ideation. Higher counts without suicidal ideation = better outcome.
Time frame: Week 4, Week 12, Week 24/Early Termination, Week 28
Population: Safety Population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 4 | With Suicidal Ideation | 0 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 4 | Without Suicidal Ideation | 260 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 12 | With Suicidal Ideation | 1 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 12 | Without Suicidal Ideation | 224 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 24/EarlyTermination | With Suicidal Ideation | 0 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 24/EarlyTermination | Without Suicidal Ideation | 271 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 28 | With Suicidal Ideation | 1 Participants |
| G-ER 1800 mg | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 28 | Without Suicidal Ideation | 256 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 28 | Without Suicidal Ideation | 243 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 4 | With Suicidal Ideation | 0 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 24/EarlyTermination | With Suicidal Ideation | 1 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 4 | Without Suicidal Ideation | 257 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 28 | With Suicidal Ideation | 0 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 12 | With Suicidal Ideation | 0 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 24/EarlyTermination | Without Suicidal Ideation | 266 Participants |
| Sugar Pill | Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS). | Patients Taking C-SSRS at Week 12 | Without Suicidal Ideation | 215 Participants |