A Study of Efficacy and Safety of Sepranolone (UC1010) in Patients With Premenstrual Dysphoric Disorder (PMDD)

A Phase II, Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study Investigating Efficacy and Safety of Sepranolone (UC1010) in Patients With Premenstrual Dysphoric Disorder (PMDD)

The objective of this phase IIb study is to evaluate the effect and safety of Sepranolone (UC1010) on premenstrual symptoms in women with Premenstrual Dysphoric Disorder (PMDD). Patients will be taking Sepranolone or Placebo (blinded to patient and study doctor) during the two weeks preceding the menstruation of three menstrual cycles. Effect (change from baseline) will be assessed by comparison of symptoms recorded daily by the patients using a validated rating scale for assessment of PMDD symptoms. Sepranolone is an endogenous steroid.

Study Overview

• Status: Completed
• Conditions: Premenstrual Dysphoric Disorder
• Intervention / Treatment: Drug: Sepranolone (UC1010) low dose; Drug: Sepranolone (UC1010) high dose; Drug: Placebo

Detailed Description

The objective of this phase IIb study is to evaluate the effect and safety of two doses of Sepranolone (UC1010) on premenstrual symptoms in women with Premenstrual Dysphoric Disorder (PMDD) in comparison to placebo, administrated during the luteal phase of three consecutive menstrual cycles. Effect will be assessed by comparison of symptoms recorded daily by the patients using a validated rating scale for assessment of PMDD symptoms and impairment of symptoms on daily life of the patients. The scale is Daily Record of Severity of Problems (DRSP). Preceding the treatment period, the diagnosis of PMDD will be established in the study participants by at lest two menstrual cycles of prospective DRSP ratings by the patients. This period will also constitute the baseline data. The effect of study medication will be assessed as the change in symptoms from baseline to during treatment. The Total symptom score of the DRSP will constitute the primary variable and the late luteal phase ratings in the respective menstrual cycles, before and during treatment, will be used.

The study will also include a follow-up (no treatment) cycle before patients final visit.

The study is conducted in four European countries (Sweden, Germany, Poland and United Kingdom) and will include up to 225 patients.

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bad Homburg, Germany
    • Zentrum für Klinische Forschnung
  • Berlin, Germany
    • Emovis
  • Essen, Germany
    • Medizentrum Essen Borbeck
  • Karlsruhe, Germany
    • Klinische Forschung Karlsruhe GmbH
  • Nürnberg, Germany
    • Praxis Dr. Steinwachs
• Poland
  • Elbląg, Poland
    • Centrum Kliniczno-Badawcze
  • Katowice, Poland
    • Centrum Medyczne Angelius Provita
  • Kraków, Poland
    • ProCreative
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
• United Kingdom
  • Liverpool, United Kingdom
    • Liverpool Women's NHS Foundation Trust
  • London, United Kingdom
    • Imperial College London
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Obstetrics and Gynaecology Keele University School of Medicine and University Hospitals of North Staffordshire

Participation Criteria

Eligibility Criteria

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

Description

Main Inclusion Criteria:

• have PMDD according to DSM-5 verified in two menstrual cycles
• have a regular menstrual cycle of 24-35 days cycle,
• use double barrier contraception, non-hormonal IUD, be truly sexually abstinent, or subject or her partner has been surgically sterilized,

Main Exclusion Criteria:

• steroid hormonal treatment or treatment with psychopharmaceuticals during previous three months
• treatments for premenstrual syndrome (PMS) or PMDD
• history of or significant medical condition ongoing
• be pregnant or plan a pregnancy within the study period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sepranolone (UC1010) low dose; Sepranolone (UC1010) low dose administered subcutaneously (SC) during the luteal phase	Drug: Sepranolone (UC1010) low dose; Subcutaneous (SC) administration
Experimental: Sepranolone (UC1010) high dose; Sepranolone (UC1010) high dose administered subcutaneously (SC) during the luteal phase	Drug: Sepranolone (UC1010) high dose; Subcutaneous (SC) administration
Placebo Comparator: Placebo; Placebo administered subcutaneously (SC) during the luteal phase	Drug: Placebo; Subcutaneous (SC) adminstration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on DRSP Total symptom score	Change in DRSP Total symptom score (Daily Record of Severity of Problems) measured during the luteal phase (i.e. the week before menstruation) before and during treatment	Baseline luteal phase score (average from two menstrual cycles) vs. luteal phase score during treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Recording of adverse events	Starting from first dose given until 1 months after treatment stop

Collaborators and Investigators

• Sponsor: Asarina Pharma
• Collaborators: Ergomed
• Investigators: Principal Investigator: Shaughn O'Brien, MD, Obstetrics and Gynaecology Keele University School of Medicine and University Hospitals of North Staffordshire

Publications and helpful links

General Publications

• Bixo M, Ekberg K, Poromaa IS, Hirschberg AL, Jonasson AF, Andreen L, Timby E, Wulff M, Ehrenborg A, Backstrom T. Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial. Psychoneuroendocrinology. 2017 Jun;80:46-55. doi: 10.1016/j.psyneuen.2017.02.031. Epub 2017 Mar 1.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2018
• Primary Completion (Actual): July 28, 2020
• Study Completion (Actual): October 23, 2020

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 27, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Syndrome; Premenstrual Dysphoric Disorder; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics; Pregnanolone
• Other Study ID Numbers: UM203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No