Phase 2
N=22
Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain
Endometriosis-related Pain
Bottom Line
View on ClinicalTrials.gov: NCT03692403 ↗Enrolled (actual)
22
Serious AEs
0.0%
Results posted
Aug 2023
Primary outcome: Primary: Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain. — -0.66; -2.04; -2.14; -3.68 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Quinagolide 360 µg (Drug); Quinagolide 720 µg (Drug); Quinagolide 1080 µg (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Ferring Pharmaceuticals
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain. |
-0.33; -1.42; -0.51; -1.97; -0.79; -2.39 | — |
| SECONDARY 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 |
-0.51; -3.70; -2.54; -4.90; -0.69; -2.04 | — |
| SECONDARY Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain. |
-0.33; -1.42; -0.51; -1.97; -0.79; -2.39 | — |
| SECONDARY Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dysmenorrhea. |
-1.10; -1.48; -0.61; -4.40; -0.95; -1.76 | — |
| SECONDARY Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Non-menstrual Pelvic Pain. |
-0.09; -1.45; -0.61; -1.42; -0.69; -2.71 | — |
| SECONDARY Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dyspareunia on Days With Sexual Intercourse. |
-1.62; -0.49; -1.69; -1.00; -1.43; -0.06 | — |
| SECONDARY Frequency of Avoiding Sexual Intercourse Due to Expected Pain |
36; 46; 41; 24; 103; 94 | — |
| SECONDARY 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. |
-0.27; -1.45; -0.31; -1.77; -0.53; -2.19 | — |
| SECONDARY Changes in the Mean Weekly Scores of the Endometriosis Health Profile-30 (EHP-30) Pain Impact Domain. |
-5.54; -5.54; -7.03; -26.66; -5.69; -13.53 | — |
| SECONDARY Changes in Vaginal Bleeding Pattern - Number of Days With Bleeding Related to Period |
38; 37; 42; 15; 11; 0 | — |
| SECONDARY Changes in Vaginal Bleeding Pattern. |
91; 101; 144; 56; 18; 9 | — |
| SECONDARY Percentage of Days With Mild and/or Strong Rescue Analgesics Used |
41.68; 26.04; 44.82; 3.57; 41.68; 22.41 | — |
| SECONDARY Total and Average Doses of Mild and/or Strong Rescue Analgesics Used |
8400.0; 5680.0; 14514.3; 1200.0; 325.10; 213.27 | — |
| SECONDARY Responder Rate |
20.0; 50.0; 33.3; 100; 0; 75.0 | — |
| SECONDARY Changes in the Mean Individual and Total Symptom and Sign Severity Scores |
-1.0; -3.0; -2.4; -5.0; -1.7; -1.5 | — |
| SECONDARY Changes in the Endometriosis Health Profile-30 (EHP-30) Scores |
-7.2; -12.8; -8.8; -39.5; -2.0; -12.0 | — |
| SECONDARY Changes in Patient Global Impression of Severity (PGIS) Scores |
2; 1; 3; 0; 2; 3 | — |
| SECONDARY Patient Global Impression of Change (PGIC) Scores |
0; 1; 0; 2; 1; 1 | — |
| SECONDARY Plasma Concentration of Quinagolide and Metabolites |
3.04; 7.77; 10.5; 1.84; 2.36; 7.10 | — |
| SECONDARY Serum Levels of Mid-luteal Phase Progesterone |
8.29; 8.49; 7.04; 8.57; 9.55; 6.00 | — |
| SECONDARY Number of Subjects With Serum Mid-luteal Progesterone Levels ≥25 Nmol/L (7.9 ng/ml) |
2; 2; 4; 1; 4; 3 | — |
| SECONDARY Serum Levels of Estradiol |
328.2; 534.4; 350.0; 431.6; 415.6; 278.8 | — |
| SECONDARY Serum Levels of Prolactin |
8.0; 13.2; 10.0; 13.4; 10.7; 11.3 | — |
| SECONDARY Serum Levels of Thyrotropin (TSH) |
1.9; 2.1; 1.3; 2.7; 1.7; 2.1 | — |
| SECONDARY Serum Levels of Insulin-like Growth Factor-1 (IGF-1) |
216.7; 221.1; 166.2; 188.7; 211.5; 208.3 | — |
| SECONDARY Changes in Bone Turnover Markers, Determined by Bone Resorption Marker Serum C-terminal Crosslinking Telopeptide of Type 1 Collagen (s-CTx) |
-0.060; 0.277; 0.067; -0.031 | — |
| SECONDARY Changes in Bone Turnover Markers, Determined by Bone Formation Marker Serum Procollagen Type I N Propeptide (s-PINP) |
-1.4; -3.5; 10.3; -21.0 | — |
| SECONDARY Changes in ECG Parameters Including PR Interval at Cycle 4 |
-1.8; 8.0; 1.0; -2.5 | — |
| SECONDARY Changes in ECG Parameters Including QRS Duration at Cycle 4 |
-0.2; 5.0; 2.8; -7.5 | — |
| SECONDARY Changes in ECG Parameters Including QT Interval at Cycle 4 |
-1.2; -7.5; 18.0; 7.0 | — |
| SECONDARY Changes in ECG Parameters Including QTcF Interval at Cycle 4 |
-6.2; 1.5; 3.2; -17.5 | — |
| SECONDARY Proportion of Subjects With Abnormal Clinically Significant Echocardiography Findings Indicating Valvular Heart Disease |
0; 0; 0; 0 | — |
| SECONDARY Proportion of Subjects Identified With Potential Impulse Control Disorders |
1; 0; 0; 0 | — |
| SECONDARY Frequency and Intensity of Adverse Events |
4; 3; 5; 2; 4; 2 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Albumin |
-0.5; 0.5; -2.8; -3.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Alkaline Phosphatase |
-16.5; 26.5; -7.2; -13.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Alanine Aminotransferase |
-8.3; 46.0; -5.8; -3.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Aspartate Aminotransferase |
-5.3; 26.5; -0.6; 4.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Bicarbonate |
-0.8; 0.5; -0.2; -2.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Direct Bilirubin |
0.0; 0.0; -0.7; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Bilirubin |
1.3; 4.3; -2.1; 1.7 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Calcium |
0.0; 0.0; -0.1; -0.1 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Cholesterol |
0.7; 0.5; 0.1; -0.1 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Chloride |
0.8; 1.0; 1.4; 2.5 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Creatinine |
-3.3; -10.6; 0.0; 0.9 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Gamma Glutamyl Transferase |
-3.5; 11.0; -2.8; -9.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Glucose |
-0.3; -0.6; -0.1; 4.8 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Potassium |
-0.2; -0.1; -0.3; -0.5 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Lactate Dehydrogenase |
-11.8; 35.0; -16.0; 8.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Phosphate |
0.1; -0.1; 0.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Protein |
-0.8; 0.0; -3.4; -5.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Sodium |
1.5; -1.5; 1.2; 0.5 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Urate |
-5.9; -23.8; 10.7; 41.6 | — |
| SECONDARY Changes in Circulating Levels of Clinical Chemistry Parameters: Urea Nitrogen |
0.3; -2.0; -0.4; -0.7 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Basophils Absolute |
-0.3; -0.4; 0.0; 0.1 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Basophils |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils Absolute |
-0.6; -0.3; -1.4; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils |
-0.1; -0.1; 0.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Hematocrit |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Hemoglobin |
1.3; -1.5; -6.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes Absolute |
2.5; -0.6; -2.1; 3.9 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes |
0.3; -0.2; -0.1; 0.3 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Hemoglobin |
0.3; 0.0; -0.2; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular HGB Concentration |
0.2; 0.3; -0.1; 1.2 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Volume |
0.0; 0.5; 0.2; -3.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes Absolute |
-2.1; -2.2; -0.1; 0.6 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes |
-0.2; -0.2; 0.0; 0.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils Absolute |
0.6; 3.4; 3.7; -4.6 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils |
0.3; 0.0; 0.1; -0.3 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Platelets |
-10.3; 36.5; 1.8; 12.0 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Erythrocytes |
-0.1; -0.1; -0.2; -0.1 | — |
| SECONDARY Changes in Circulating Levels of Clinical Haematology Parameters: Leukocytes |
0.3; -0.5; 0.0; 0.0 | — |
| SECONDARY Urinalysis Parameters (Protein, Glucose, Bilirubin, pH, Nitrite, Ketone, Urobilinogen, Blood, Leukocytes, and Specific Gravity) |
1; 1; 2; 2; 0; 0 | — |
| SECONDARY Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Chemistry Parameters |
0; 0; 0; 0 | — |
| SECONDARY Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Haematology Parameters |
0; 0; 0; 0 | — |
| SECONDARY Proportion of Subjects With Markedly Abnormal Changes in Urinalysis Parameters |
0; 0; 0; 0 | — |
| SECONDARY Frequency and Intensity of Ring Acceptability Parameters: Insertion of the Vaginal Ring |
2; 3; 6; 2; 3; 2 | — |
| SECONDARY Frequency and Intensity of Ring Acceptability Parameters: Removal of the Vaginal Ring |
6; 5; 6; 2; 0; 0 | — |
| SECONDARY Frequency and Intensity of Ring Acceptability Parameters: Felt the Ring |
0; 1; 3; 1; 6; 2 | — |
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.
Data sourced from ClinicalTrials.gov (NCT03692403). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.