Randomized Trial Assessing Quinagolide Vaginal Ring for Endometriosis-related Pain

Endometriosis-related Pain Clinical Trial

— RAQUEL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03692403
• Other study ID #: 000165
• Status: Completed
• Phase: Phase 2
• Start date: December 26, 2018
• Est. completion date: February 14, 2022

Study information

• Verified date: October 2022
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 14, 2022
• Est. primary completion date: February 14, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Endometriosis
• Endometriosis-related Pain

Intervention

Drug:
• Quinagolide 360 µg
Vaginal ring containing quinagolide 360 µg for daily releases
• Quinagolide 720 µg
Vaginal ring containing quinagolide 720 µg for daily releases
• Quinagolide 1080 µg
Vaginal ring containing quinagolide 1080 µg for daily releases
• Placebo
Matching placebo

Locations

Country	Name	City	State
United States	The Iowa Clinic	Ankeny	Iowa
United States	Austin Area Ob, Gyn and Fertility	Austin	Texas
United States	Johns Hopkins Outpatient Center	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Main Line Fertility Center	Bryn Mawr	Pennsylvania
United States	Clinical Trials of South Carolina	Charleston	South Carolina
United States	PMG Research of Charlotte	Charlotte	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Corpus Christi Women's Clinic	Corpus Christi	Texas
United States	Omega Research Consultants	DeBary	Florida
United States	Carolina's Women's Research and Wellness Center	Durham	North Carolina
United States	UConn Health Lowell P Weicker Jr Clinical Research Center	Farmington	Connecticut
United States	Rapha Institute For Clinical Research	Fayetteville	North Carolina
United States	Onyx Clinical Research	Flint	Michigan
United States	Penn State Health - Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Advances in Health, Inc.	Houston	Texas
United States	Arkansas Primary Care Clinic	Little Rock	Arkansas
United States	Advance Clinical Research	Meridian	Idaho
United States	Marchand Institute for Minimally Invasive Surgery	Mesa	Arizona
United States	Southern Clinical Research Associates	Metairie	Louisiana
United States	Florida Research Center	Miami	Florida
United States	Miami Dade Medical Research Institute	Miami	Florida
United States	South Florida Research Center	Miami	Florida
United States	Vista Health Research	Miami	Florida
United States	Yale Fertility Center	New Haven	Connecticut
United States	Advanced Research Institute	New Port Richey	Florida
United States	Tidewater Clinical Research, Inc.	Norfolk	Virginia
United States	OB/GYN Specialists of Richmond	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Valley OB/GYN Clinic, PC	Saginaw	Michigan
United States	Meridien Research	Saint Petersburg	Florida
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	Medical Center for Clinical Research	San Diego	California
United States	Physician Care Clinical Research	Sarasota	Florida
United States	Omni Fertility Clinical Research LLC	Shreveport	Louisiana
United States	OB/Gyn Associates	Silver Spring	Maryland
United States	Southern Illinois University	Springfield	Illinois
United States	Center of Reproductive Medicine LLC	Webster	Texas
United States	OB•GYN Associates of WNY	West Seneca	New York
United States	Cypress Medical Research Center	Wichita	Kansas
United States	Lyndhurst Clinical Research	Winston-Salem	North Carolina
United States	Unified Women's Clinical Research d/b/a Lyndhurst Clinical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes from baseline to cycle 4.	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
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	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Days with menstrual bleeding (dysmenorrhea). No menstrual bleeding (non-menstrual pelvic pain) Changes from baseline to cycle 4	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Endometriosis-related Pain.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes over 4 menstrual cycles	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dysmenorrhea.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes over 4 menstrual cycles	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Non-menstrual Pelvic Pain.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes over 4 menstrual cycles	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Daily Numerical Rating Scale (NRS) Scores for the Worst Dyspareunia on Days With Sexual Intercourse.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes over 4 menstrual cycles.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Frequency of Avoiding Sexual Intercourse Due to Expected Pain	The participants recorded daily if they had sexual intercourse, in an e-diary. For the days when participants did not have intercourse, the participant recorded if the reason for not having intercourse was because they expected pain: "Yes" (I did not have intercourse this day, because I expected pain) or "No" (I did not have intercourse this day, but this was not because I expected pain). The numbers represent the cumulative number of days with no intercourse, summed across all participants.; In some cases, there are missing data as not every participant completed the e-diary for 100% of study days.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
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.	Assessed daily by participants in an e-Diary. NRS is an 11-point scale, with 0 indicating no pain and 10 indicating the worst imaginable pain.; Changes over 4 menstrual cycles.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Weekly Scores of the Endometriosis Health Profile-30 (EHP-30) Pain Impact Domain.	Assessed weekly by participants in an e-Diary. EHP-30 is a quality-of-life questionnaire. Score ranges from 0-100 and lower score denotes improvement.; Changes over 4 menstrual cycles.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in Vaginal Bleeding Pattern - Number of Days With Bleeding Related to Period	The participants recorded daily if they had any vaginal bleeding during the past 24 hours, in an e-diary. Of the participants who had a bleeding, the participant recorded if this was menstrual bleeding: "Yes" (I had a vaginal bleeding that was menstrual bleeding) or "No" (I had a vaginal bleeding that was not menstrual bleeding). The numbers represent the cumulative number of days with vaginal bleeding, summed across all participants.; In some cases, there are missing data as not every participant completed the e-diary for 100% of study days.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in Vaginal Bleeding Pattern.	The participants recorded daily if they had any vaginal bleeding during the past 24 hours, in an e-diary. Of the participants who had a bleeding, the participant recorded the assessed bleeding volume as either spotting (tiny amount of blood on underwear or panty liners), light bleeding (requiring 1-3 sanitary pads or tampons per day), moderate bleeding (requiring 4-6 sanitary pads or tampons per day), or heavy bleeding (requiring more than 6 sanitary pads or tampons per day). The numbers represent the cumulative number of days with vaginal bleeding, summed across all participants.; In some cases, there are missing data as not every participant completed the e-diary for 100% of study days.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Percentage of Days With Mild and/or Strong Rescue Analgesics Used	Assessed daily by participants in an e-Diary	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Total and Average Doses of Mild and/or Strong Rescue Analgesics Used	Assessed daily by participants in an e-Diary	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Responder Rate	Assessed as =30%, =50% and =70% reduction from the baseline in mean daily NRS score for the worst endometriosis-related pain, dysmenorrhea and non-menstrual pelvic pain and for the worst endometriosis-related pain impact	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Mean Individual and Total Symptom and Sign Severity Scores	Assessed by the Biberoglu and Behrman (B&B) scale which is a 4-point scale with 0=none and 3=severe.; The scores are the mean individual scores.; The B&B scale consists of two parts. The first part of the B&B scale evaluates symptoms of endometriosis (i.e. pain). There are 3 subscales: pelvic pain(A, 0=none and 3=severe), dysmenorrhea (B, 0=none and 3=severe), and dyspareunia(C, 0=none and 3=severe). The total pelvic pain score is the sum of the three scores, i.e. A+B+C, which can range from 0 to 9. The second part of the B&B scale evaluates signs of endometriosis. There are 2 subscales pelvic tenderness (D, 0=none and 3=severe) and induration (E, 0=none and 3=severe) based on findings from a pelvic examination. The total physical pain score is the sum of the two scores, i.e. D+E, which can range from 0 to 6. The total symptom and sign severity score is the sum of all five scores, i.e. A+B+C+D+E, which can range from 0 to 15.; The values are the change from baseline to cycle 4.	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in the Endometriosis Health Profile-30 (EHP-30) Scores	Assessed by the EHP-30 quality-of-life questionnaire completed by participants. Score ranges from 0-100 with lower score denoting improvement.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in Patient Global Impression of Severity (PGIS) Scores	Assessed by the PGIS scale completed by participants. PGIS is a 6-point scale depicting a participant's rating of their current conditions from "good" to "bad".; It ranges from 0 (none) to 5 (very severe).	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Patient Global Impression of Change (PGIC) Scores	Assessed by the PGIC scale completed by participants. PGIC is a 7-point scale depicting a patient's rating of their overall improvement from "good" to "bad".	At cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Plasma Concentration of Quinagolide and Metabolites	Assessed by blood samples collection	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)
Secondary	Serum Levels of Mid-luteal Phase Progesterone	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Number of Subjects With Serum Mid-luteal Progesterone Levels =25 Nmol/L (7.9 ng/ml)	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Serum Levels of Estradiol	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Serum Levels of Prolactin	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Serum Levels of Thyrotropin (TSH)	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Serum Levels of Insulin-like Growth Factor-1 (IGF-1)	Assessed by blood samples collection	At baseline and cycle 4 (around 3.5 months, each cycle is approximately 28 days)
Secondary	Changes in Bone Turnover Markers, Determined by Bone Resorption Marker Serum C-terminal Crosslinking Telopeptide of Type 1 Collagen (s-CTx)	Assessed by blood samples collection. Changes from baseline to cycle 4	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in Bone Turnover Markers, Determined by Bone Formation Marker Serum Procollagen Type I N Propeptide (s-PINP)	Assessed by blood samples collection. Changes from baseline to cycle 4	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in ECG Parameters Including PR Interval at Cycle 4	Assessed by 12-lead ECG	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in ECG Parameters Including QRS Duration at Cycle 4	Assessed by 12-lead ECG	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in ECG Parameters Including QT Interval at Cycle 4	Assessed by 12-lead ECG	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Changes in ECG Parameters Including QTcF Interval at Cycle 4	Assessed by 12-lead ECG	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Proportion of Subjects With Abnormal Clinically Significant Echocardiography Findings Indicating Valvular Heart Disease	Assessed by echocardiography.; Each echocardiography was to be assessed as normal or abnormal according to American College of Cardiology/American Heart Association guidelines for valvular heart disease. If abnormal, the level of valvular regurgitation and valvular stenosis was specified as mild, moderate or severe and valvular structure was evaluated as well.; Measured at cycle 4.	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Proportion of Subjects Identified With Potential Impulse Control Disorders	Assessed by the questionnaire for impulsive-compulsive disorders completed by participants.; Measured at cycle 4.	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Frequency and Intensity of Adverse Events	Assessed by an Adverse Events Log completed by the Investigator	From signing informed consent through study completion, around 8 months
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Albumin	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Alkaline Phosphatase	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Alanine Aminotransferase	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Aspartate Aminotransferase	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Bicarbonate	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Direct Bilirubin	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Bilirubin	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Calcium	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Cholesterol	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Chloride	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Creatinine	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Gamma Glutamyl Transferase	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Glucose	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Potassium	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Lactate Dehydrogenase	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Phosphate	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Protein	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Sodium	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Urate	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Chemistry Parameters: Urea Nitrogen	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Basophils Absolute	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Basophils	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils Absolute	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Eosinophils	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Hematocrit	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Hemoglobin	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes Absolute	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Lymphocytes	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Hemoglobin	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular HGB Concentration	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Ery. Mean Corpuscular Volume	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes Absolute	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Monocytes	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils Absolute	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Neutrophils	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Platelets	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Erythrocytes	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Changes in Circulating Levels of Clinical Haematology Parameters: Leukocytes	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Urinalysis Parameters (Protein, Glucose, Bilirubin, pH, Nitrite, Ketone, Urobilinogen, Blood, Leukocytes, and Specific Gravity)	Assessed by urine sample collection (dip-stick test). Overall Urinalysis Result.	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Chemistry Parameters	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Proportion of Subjects With Markedly Abnormal Changes in Circulating Levels of Clinical Haematology Parameters	Assessed by blood samples collection	At baseline and at menstrual cycle 4 (around 4 months)
Secondary	Proportion of Subjects With Markedly Abnormal Changes in Urinalysis Parameters	Assessed by urine samples collection	At baseline and at menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Frequency and Intensity of Ring Acceptability Parameters: Insertion of the Vaginal Ring	Assessed by a questionnaire completed by participants, addressing ring insertion	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Frequency and Intensity of Ring Acceptability Parameters: Removal of the Vaginal Ring	Assessed by a questionnaire completed by participants, addressing ring removal.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)
Secondary	Frequency and Intensity of Ring Acceptability Parameters: Felt the Ring	Assessed by a questionnaire completed by participants, addressing any feeling of the ring while the ring is in the body.	From baseline to menstrual cycle 4 (around 4 months, each cycle is approximately 28 days)