Trial Outcomes & Findings for Quinagolide Vaginal Ring on Lesion Reduction Assessed by MRI in Women With Endometriosis/Adenomyosis (NCT NCT03749109)

Results Overview

The MRI examination was performed on a high resolution 3T machine at screening and at end-of-treatment / cycle 4. At screening, every measurable lesion (defined as ≥10 mm in size) of any type was recorded and was summed up by type for primary analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)

Results posted on

2023-08-07

Participant Flow

The trial was performed in 6 investigational sites in 3 countries between Aug 2019 to Jul 2021.

In total, 147 subjects were screened. Of these, 80 were screening failures and 67 were randomized and exposed to the investigational medicinal product (IMP): 35 to Quinagolide and 32 to Placebo.

Participant milestones

Participant milestones
Measure	Quinagolide 1080 µg Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo Vaginal ring containing matching placebo Placebo: Matching placebo
Overall Study STARTED	35	32
Overall Study COMPLETED	33	32
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Quinagolide 1080 µg Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo Vaginal ring containing matching placebo Placebo: Matching placebo
Overall Study Adverse Event	2	0

Baseline Characteristics

Quinagolide Vaginal Ring on Lesion Reduction Assessed by MRI in Women With Endometriosis/Adenomyosis

Outcome measures
Measure	Quinagolide 1080 µg n=35 Participants Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=31 Participants Vaginal ring containing matching placebo Placebo: Matching placebo
Changes in Clinical Chemistry and Hematology Parameters: Urea Nitrogen	-0.180 mmol/L Standard Deviation 1.0184	0.148 mmol/L Standard Deviation 1.2286

SECONDARY outcome

Timeframe: At baseline and at menstrual cycle 4 (around 5 months, each cycle is approximately 28 days)

Assessed by blood sample collection

Outcome measures

Outcome measures
Measure	Quinagolide 1080 µg n=35 Participants Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=32 Participants Vaginal ring containing matching placebo Placebo: Matching placebo
Proportion of Subjects With Markedly Abnormal Changes in Clinical Chemistry and Hematology Parameters	2.86 Percentage of subjects	0 Percentage of subjects

SECONDARY outcome

Timeframe: From obtaining the informed consent to end of trial (up to 6 menstrual cycles ~ around 6 months, each cycle is approximately 28 days)

Assessed by and Adverse Event Log completed by the Investigator

Outcome measures

Outcome measures
Measure	Quinagolide 1080 µg n=35 Participants Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=32 Participants Vaginal ring containing matching placebo Placebo: Matching placebo
Frequency and Intensity of Adverse Events Mild adverse events	28.6 Percentage of subjects	43.8 Percentage of subjects
Frequency and Intensity of Adverse Events Moderate adverse events	42.9 Percentage of subjects	37.5 Percentage of subjects
Frequency and Intensity of Adverse Events Severe adverse events	2.9 Percentage of subjects	9.4 Percentage of subjects

Adverse Events

Quinagolide 1080 µg

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Quinagolide 1080 µg n=35 participants at risk Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=32 participants at risk Vaginal ring containing matching placebo Placebo: Matching placebo
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 1/35 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	0.00% 0/32 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.

Other adverse events

Additional Information

Global Clinical Compliance

Ferring Pharmaceuticals

Phone: -

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
Publication restrictions are in place

Restriction type: OTHER

Measure	Quinagolide 1080 µg n=35 Participants Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=32 Participants Vaginal ring containing matching placebo Placebo: Matching placebo	Total n=67 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	36.9 years STANDARD_DEVIATION 5.51 • n=5 Participants	35.2 years STANDARD_DEVIATION 5.96 • n=7 Participants	36.1 years STANDARD_DEVIATION 5.75 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	32 Participants n=7 Participants	66 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	23.91 kg/m^2 STANDARD_DEVIATION 3.86 • n=5 Participants	23.30 kg/m^2 STANDARD_DEVIATION 4.15 • n=7 Participants	23.62 kg/m^2 STANDARD_DEVIATION 3.98 • n=5 Participants

Measure	Quinagolide 1080 µg n=35 participants at risk Vaginal ring containing Quinagolide 1080 µg, with daily target release rate of 13.5 µg. Quinagolide 1080 µg: Vaginal ring containing Quinagolide 1080 µg for daily releases	Placebo n=32 participants at risk Vaginal ring containing matching placebo Placebo: Matching placebo
Nervous system disorders Dizziness	2.9% 1/35 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	12.5% 4/32 • Number of events 4 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Nervous system disorders Somnolence	5.7% 2/35 • Number of events 4 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	3.1% 1/32 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Gastrointestinal disorders Nausea	8.6% 3/35 • Number of events 3 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	6.2% 2/32 • Number of events 3 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Gastrointestinal disorders Abdominal distension	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	3.1% 1/32 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/35 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	6.2% 2/32 • Number of events 4 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
General disorders Fatigue	2.9% 1/35 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	6.2% 2/32 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
General disorders Peripheral swelling	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	3.1% 1/32 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
General disorders Pyrexia	5.7% 2/35 • Number of events 5 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	0.00% 0/32 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Infections and infestations Nasopharyngitis	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	3.1% 1/32 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Infections and infestations Corona virus infection	0.00% 0/35 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	6.2% 2/32 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Nervous system disorders Headache	17.1% 6/35 • Number of events 9 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	25.0% 8/32 • Number of events 15 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Nervous system disorders Hypoaesthesia	0.00% 0/35 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	6.2% 2/32 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Reproductive system and breast disorders Ovarian cyst	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	3.1% 1/32 • Number of events 1 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Reproductive system and breast disorders Vulvovaginal pruritus	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	0.00% 0/32 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.
Vascular disorders Hot flush	5.7% 2/35 • Number of events 2 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.	0.00% 0/32 • Adverse events were recorded for each participant from the time of signed informed consent for participation in the trial to follow-up visit (approximately 1 month after visit 8 (month 4), up to 5 months). All adverse events with onset after start of first administration of IMP and before the follow-up phone call were considered treatment-emergent.