A Clinical Trial of Intravenous (IV) Ganaxolone in Women With Postpartum Depression

A Phase 2A, Double-blind, Placebo-controlled, Multiple-dose Escalation Study to Evaluate Safety, Pharmacokinetics and Efficacy of Intravenously Administered Ganaxolone in Women With Postpartum Depression

This study will evaluate the Safety, Pharmacokinetics and Efficacy of IV Administration of Ganaxolone in Women with Postpartum Depression

Study Overview

• Status: Completed
• Conditions: Behavioral Symptoms; Mental Disorders; Depressive Disorder; Depression; Mood Disorders; Pregnancy Complications; Depression, Postpartum; Puerperal Disorders; Postpartum; PPD
• Intervention / Treatment: Drug: Placebo; Drug: Ganaxolone

Detailed Description

This study will explore whether ganaxolone is safe and well tolerated in women suffering from PPD. In addition, ganaxolone's efficacy in treating depressive symptoms will be assessed through a set of exploratory analyses. Plasma levels of ganaxolone will be determined through pharmacokinetic analysis. The study results will be used to select a ganaxolone dose and dosing regimen for further development in PPD.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Marinus Research Site
  • California
    • Costa Mesa, California, United States, 92626
      • Marinus Research Site
    • Lemon Grove, California, United States, 91945
      • Marinus Research Site
    • San Diego, California, United States, 92103
      • Marinus Research Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Marinus Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Marinus Research Site
    • Decatur, Georgia, United States, 30030
      • Marinus Research Site
  • Kansas
    • Leawood, Kansas, United States, 66206
      • Marinus Research Site
    • Overland Park, Kansas, United States, 66211
      • Marinus Research Site
  • New York
    • New York, New York, United States, 10032
      • Marinus Research Site
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Marinus Research Site
  • Texas
    • Houston, Texas, United States, 77058
      • Marinus Research Site
    • Irving, Texas, United States, 75062
      • Marinus Research Site
  • Utah
    • Orem, Utah, United States, 84058
      • Marinus Research Site
    • Salt Lake City, Utah, United States, 84124
      • Marinus Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Marinus Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant experienced a Major Depressive Episode, which started between the start of the third trimester and 4 weeks following delivery. The Major Depressive Episode must be diagnosed according to Mini International Neuropsychiatric Interview (MINI) 7.0 interview
• Participant gave birth in the last 6 months
• Participant has a Hamilton Depression Rating Scale 17-item version (HAMD17) score of ≥ 26 at screening
• Participant must agree to stop breastfeeding from start of study treatment or must agree to temporarily cease giving breast milk to her infant(s)

Exclusion Criteria:

• Current or past history of any psychotic illness, including Major Depressive Episode with psychotic features
• History of suicide attempt within the past 3 years
• Active suicidal ideation
• History of bipolar I disorder
• History of seizure disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ganaxolone; Intravenous	Drug: Ganaxolone; Ganaxolone IV
Placebo Comparator: Placebo; Intravenous	Drug: Placebo; Placebo IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Total Score	The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline and Day 3 post-infusion (60 hours post start of infusion) for Cohorts 1 to 3 and Baseline and Day 29 for Cohort 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HAMD17 Total Score at Indicated Time Points	The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline, Day1 post-infusion(6hours post start of infusion), Day1(12hours post start of infusion), Day2(24hours post start of infusion),Day3 post-infusion(48hours post start of infusion),Day4(72hours post start of infusion),Days 8,11,15,22,36,57 and 71
Number of Participants With HAMD17 Response	HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 response is presented.	Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day 2 (24 hours post SOI),Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,36,57 and 71
Number of Participants With HAMD17 Remission	HAMD17 Remission was defined as total score ≤7. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 remission is presented	Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day2 (24 hours post SOI), Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,34,57 and 71
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score	The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline, Day 1, Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
Change From Baseline in Spielberger State-Trait Anxiety Inventory 6-item Version (STAI6) Total Score	The STAI6 is a 6-item self-rated instrument used to assess anxiety state. The STAI6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. The STAI6 score was the result of first totaling the 6 individual item scores, and then prorating by a multiplication factor of 20/6 to acquire a score range of 20 (low anxiety) to 80 (high anxiety). Higher score indicated higher level of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline, Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
Number of Participants With Response to Clinical Global Impression-Improvement (CGI-I) Scale	The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. "very much improved"; 2. "much improved"; 3. "minimally improved"; 4. "no change"; 5. "minimally worse"; 6. "much worse"; 7. "very much worse". Higher scores indicated worse condition. Response was defined as >50% decrease from Baseline in CGI-I total score.	Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals
• Investigators: Study Director: Joseph Hulihan, MD, Marinus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Actual): May 10, 2019
• Study Completion (Actual): May 10, 2020

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Postpartum Depression; Postpartum Care
• Additional Relevant MeSH Terms: Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depression; Depressive Disorder; Mental Disorders; Depression, Postpartum; Mood Disorders; Pregnancy Complications; Behavioral Symptoms; Puerperal Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Neurosteroids; Ganaxolone
• Other Study ID Numbers: 1042-PPD-2002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No