Clinical trial NCT03692403: Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial Assessing the Efficacy, Safety and Dose-response of Quinagolide Extended-release Vaginal Rings Administered Sequentially for 4 Menstrual Cycles in Women With Moderate to Severe Endometriosis-related Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometriosis-related Pain
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-10-02
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of three doses of quinagolide administered as an extended-release vaginal ring compared to placebo on reduction of moderate to severe endometriosis-related pain


Eligibility criteria: Inclusion Criteria:

* Pre-menopausal females aged ≥18 years at time of signing informed consent(s) with regular menstrual cycles.
* Body mass index (BMI) of 18-42 kg/m2 (both inclusive) at screening.
* Initial confirmation of endometriosis by laparoscopy or laparotomy within the last 10 years before the run-in visit or visualization of persistent endometrioma by repeat ultrasound.
* Transvaginal ultrasound documenting a uterus with no clinically significant abnormalities and presence of at least one ovary with no clinically significant abnormalities (with the exception of endometrioma) at the run-in visit.
* Eligible participants experienced moderate to severe endometriosis-related pain, which was defined as at the run-in visit, the participant having an NRS score of ≥5 for the worst endometriosis related pain during the past menstrual cycle and at randomization, the participant having a mean daily NRS score of ≥4 for the worst endometriosis related pain during each run-in menstrual cycle.

Exclusion Criteria:

* History of no relief of endometriosis related pain after any medical therapy or surgery. However, history of partial pain relief, discontinuation due to side effects are not exclusionary.
* Known bone diseases (e.g. osteoporosis, Paget's disease and osteomalacia) affecting bone resorption or bone formation markers.
* Any significant abnormal findings of heart examinations before randomization.
* History of mental illness including occurrence of acute psychosis, bipolar disorders and schizophrenia (except for well-controlled anxiety and/or depression with no changes to interventions for 6 months prior to start of run-in)
* History of impulse control disorders including pathological gambling, compulsive buying, hypersexuality, and binge eating or being identified with potential impulse control disorder by the questionnaire for impulsive-compulsive disorders (a score ≥2 for any sub-questions of Question 3 or a score ≥1 for any sub-questions of Question 4) prior to randomization.
* History of orthostatic hypotension or recurrent syncope.

Primary outcomes:
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain.
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary outcomes:
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain on Days With Menstrual Bleeding and for the Worst Endometriosis-related Pain on Days With no Menstrual Bleeding
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dysmenorrhea.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Non-menstrual Pelvic Pain.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dyspareunia on Days With Sexual Intercourse.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Frequency of Avoiding Sexual Intercourse Due to Expected Pain
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Impact of Endometriosis-related Pain on the Subject's Ability to Function.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Weekly Scores of the Endometriosis Health Profile-30 (EHP-30) Pain Impact Domain.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in Vaginal Bleeding Pattern - Number of Days With Bleeding Related to Period
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in Vaginal Bleeding Pattern.
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Percentage of Days With Mild and/or Strong Rescue Analgesics Used
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Total and Average Doses of Mild and/or Strong Rescue Analgesics Used
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Responder Rate
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Mean Individual and Total Symptom and Sign Severity Scores
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in the Endometriosis Health Profile-30 (EHP-30) Scores
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in Patient Global Impression of Severity (PGIS) Scores
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Patient Global Impression of Change (PGIC) Scores
timeFrame: At cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Plasma Concentration of Quinagolide and Metabolites
timeFrame: Within 5 days after first ring insertion and at around 1 month, 3 months, 3.5 months and 4 months after baseline (each cycle is approximately 28 days)
measure: Serum Levels of Mid-luteal Phase Progesterone
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Number of Subjects With Serum Mid-luteal Progesterone Levels ≥25 Nmol/L (7.9 ng/ml)
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Serum Levels of Estradiol
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Serum Levels of Prolactin
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Serum Levels of Thyrotropin (TSH)
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Serum Levels of Insulin-like Growth Factor-1 (IGF-1)
timeFrame: At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
measure: Changes in Bone Turnover Markers, Determined by Bone Resorption Marker Serum C-terminal Crosslinking Telopeptide of Type 1 Collagen (s-CTx)
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in Bone Turnover Markers, Determined by Bone Formation Marker Serum Procollagen Type I N Propeptide (s-PINP)
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in ECG Parameters Including PR Interval at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in ECG Parameters Including QRS Duration at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in ECG Parameters Including QT Interval at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Changes in ECG Parameters Including QTcF Interval at Cycle 4
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Proportion of Subjects With Abnormal Clinically Significant Echocardiography Findings Indicating Valvular Heart Disease
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Proportion of Subjects Identified With Potential Impulse Control Disorders
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Frequency and Intensity of Adverse Events
timeFrame: From signing informed consent through study completion, around 8 months
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Albumin
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Alkaline Phosphatase
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Alanine Aminotransferase
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Aspartate Aminotransferase
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Bicarbonate
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Direct Bilirubin
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Bilirubin
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Calcium
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Cholesterol
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Chloride
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Creatinine
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Gamma Glutamyl Transferase
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Glucose
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Potassium
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Lactate Dehydrogenase
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Phosphate
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Protein
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Sodium
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Urate
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters: Urea Nitrogen
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Basophils Absolute
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Basophils
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils Absolute
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Hematocrit
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Hemoglobin
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes Absolute
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Hemoglobin
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular HGB Concentration
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Volume
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes Absolute
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils Absolute
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Platelets
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Erythrocytes
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Changes in Circulating Levels of Clinical Haematology Parameters: Leukocytes
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Urinalysis Parameters (Protein, Glucose, Bilirubin, pH, Nitrite, Ketone, Urobilinogen, Blood, Leukocytes, and Specific Gravity)
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Chemistry Parameters
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Haematology Parameters
timeFrame: At baseline and at menstrual cycle 4 (around 4 months)
measure: Proportion of Subjects With Markedly Abnormal Changes in Urinalysis Parameters
timeFrame: At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Frequency and Intensity of Ring Acceptability Parameters: Insertion of the Vaginal Ring
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Frequency and Intensity of Ring Acceptability Parameters: Removal of the Vaginal Ring
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
measure: Frequency and Intensity of Ring Acceptability Parameters: Felt the Ring
timeFrame: From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Marchand Institute for Minimally Invasive Surgery
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic
state: Arkansas
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Farmington
country: United States
facility: UConn Health Lowell P Weicker Jr Clinical Research Center
state: Connecticut
city: New Haven
country: United States
facility: Yale Fertility Center
state: Connecticut
city: DeBary
country: United States
facility: Omega Research Consultants
state: Florida
city: Miami
country: United States
facility: South Florida Research Center
state: Florida
city: Miami
country: United States
facility: Florida Research Center
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute
state: Florida
city: Miami
country: United States
facility: Vista Health Research
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research
state: Florida
city: Meridian
country: United States
facility: Advance Clinical Research
state: Idaho
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Ankeny
country: United States
facility: The Iowa Clinic
state: Iowa
city: Wichita
country: United States
facility: Cypress Medical Research Center
state: Kansas
city: Metairie
country: United States
facility: Southern Clinical Research Associates
state: Louisiana
city: Shreveport
country: United States
facility: Omni Fertility Clinical Research LLC
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
city: Silver Spring
country: United States
facility: OB/Gyn Associates
state: Maryland
city: Flint
country: United States
facility: Onyx Clinical Research
state: Michigan
city: Saginaw
country: United States
facility: Valley OB/GYN Clinic, PC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: West Seneca
country: United States
facility: OB•GYN Associates of WNY
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte
state: North Carolina
city: Durham
country: United States
facility: Carolina's Women's Research and Wellness Center
state: North Carolina
city: Fayetteville
country: United States
facility: Rapha Institute For Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Unified Women's Clinical Research d/b/a Lyndhurst Clinical Research
state: North Carolina
city: Bryn Mawr
country: United States
facility: Main Line Fertility Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health - Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Austin Area Ob, Gyn and Fertility
state: Texas
city: Corpus Christi
country: United States
facility: Corpus Christi Women's Clinic
state: Texas
city: Houston
country: United States
facility: Advances in Health, Inc.
state: Texas
city: Webster
country: United States
facility: Center of Reproductive Medicine LLC
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Norfolk
country: United States
facility: Tidewater Clinical Research, Inc.
state: Virginia
city: Richmond
country: United States
facility: OB/GYN Specialists of Richmond
state: Virginia
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: