A Dose-Finding Study to Evaluate Ovarian Function and Vaginal Bleeding in Next Generation Rings (P06109/MK-8175A/MK-8342B-012)

Contraception Clinical Trial

Official title:

A Multicenter, Randomized, Partially-blinded, Phase IIb Dose-finding Study on Ovarian Function, Vaginal Bleeding Pattern, and Pharmacokinetics Associated With the Use of Combined Vaginal Rings Releasing 17β-estradiol Plus Three Different Doses of Either Nomegestrol Acetate or Etonogestrel in Healthy Women Aged 18-35 Years. Protocol MK-8175A/MK-8342B 012

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01709318
• Other study ID #: P06109
• Secondary ID: 2012-002459-41P0
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2012
• Est. completion date: October 22, 2013

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this trial was to identify at least one next generation ring (NGR) that demonstrates inhibition of ovulation (which was considered confirmed if in the subset of participants ovulation was observed in less than 15% of the participants at any time during the 3 treatment cycles of the study) and cycle control that was non-inferior to NuvaRing®, as judged by the incidence of breakthrough bleeding and/or spotting (BTB-S) during Cycle 3. The primary hypothesis was that at least 1 of the 6 NGRs would show inhibition of ovulation and cycle control during Treatment Cycle 3 that is non-inferior to NuvaRing®, as judged by the incidence of BTB-S.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 666
• Est. completion date: October 22, 2013
• Est. primary completion date: October 22, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) =18 and =35

• Regular cycles from 24 to 35 days in length, with an intra-individual variation of ±3 days permitted within this range

• Good physical and mental health

Exclusion Criteria:

• Diabetes mellitus with vascular involvement

• Presence of a severe or multiple risk factor(s) for venous or arterial thrombosis

• Severe dyslipoproteinemia

• Severe hypertension

• Presence or history of pancreatitis associated with severe hypertriglyceridaemia

• Presence or history of severe hepatic disease

• Undiagnosed vaginal bleeding

• Known or suspected pregnancy

• Participation in another investigational drug study within 30 days prior to screening visit

• History of malignancy =5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer

• Documented abnormal cervical smear result in 6 months prior to screening visit

• Sterilization using a fallopian tube occlusion device (e.g., Essure method)

• Sex hormone therapy within 2 months prior to screening visit for purpose other than contraception, or injectable hormonal contraception within 6 months prior to screening

Related Conditions & MeSH terms

• Contraception
• Uterine Hemorrhage

Intervention

Drug:
• Nomegestrol acetate (NOMAC)
Daily release of 500, 700, or 900 µg.
• Etonogestrel (ENG)
Daily release of 75, 100, 120 or 125 µg
• Ethinyl estradiol (EE)
Daily release of 15 µg
• Estradiol (E2)
Daily release of 300 µg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & Publications (1)

Duijkers I, Klipping C, Heger-Mahn D, Fayad GN, Frenkl TL, Cruz SM, Korver T. Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17beta-estradiol and the progestagens eto — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Venous or Arterial Thrombotic/Thromboembolic Events	Venous or arterial thrombotic/thrombo-embolic events, (VTEs or ATEs) (e.g., deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident) were assessed.	From Cycle 1 Day 1 up to 8 days after Day 28 of Cycle 3 (Up to ~92 days)
Primary	Percentage of Participants With Ovulation Incidence, by Cycle	Ovulation was defined as having 2 or more consecutive progesterone concentrations >16 nmol/L within 5 days, confirmed by ultrasound evidence of ovulation (follicular rupture or preceding presence of a follicle-like structure >15 mm in size).	Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
Primary	Percentage of Participants With Progesterone Concentrations >16 Nmol/L, by Cycle	Maximum progesterone (Max P) was defined as the maximum progesterone value. Ovulation was defined as 2 or more consecutive progesterone concentrations >16 nmol/L within 5 days during the 3 treatment cycles, supported by ultrasound evidence of ovulation. The Max P values greater than 16 nmol/L are presented by vaginal ring group and cycle.	Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
Primary	Percentage of Participants With Breakthrough Bleeding and/or Spotting During Cycle 3	Breakthrough bleeding and/or spotting (BTB-S) is defined as any bleeding or spotting episode that occurred during the expected non-bleeding period that was neither an early nor a continued withdrawal bleeding. Bleeding = any bloody vaginal discharge that required one or more sanitary pads or tampons per day; Spotting = any bloody vaginal discharge that required no sanitary pads or tampons per day.	Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~28 days)
Secondary	Percentage of Participants With Absence of Withdrawal Bleeding and/or Spotting During Cycle 2	Withdrawal bleeding and/or spotting is considered any bleeding or spotting episode that starts during or continues into the expected bleeding period (i.e., when the ring has been removed the last week of the cycle). Absence of withdrawal bleeding is no withdrawal bleeding and/or spotting episodes during an expected bleeding period when the ring has been removed.	Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)
Secondary	Intensity of Withdrawal Bleeding During Cycle 2	Intensity of withdrawal bleeding during Cycle 2 was defined as the ratio of the number of withdrawal bleeding days divided by the number of withdrawal bleeding and/or spotting days. Withdrawal bleeding and/or spotting is considered any bleeding or spotting episode that starts during or continues into the expected bleeding period (i.e., when the ring has been removed the last week of the cycle). Absence of withdrawal bleeding is no withdrawal bleeding and/or spotting episodes during an expected bleeding period when the ring has been removed.	Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)
Secondary	Intensity of Breakthrough Bleeding and/or Spotting During Cycle 3	Intensity of breakthrough bleeding and/or spotting (BTB-S) during Cycle 3 was defined as the ratio of the number of breakthrough bleeding days divided by the number of breakthrough bleeding and/or spotting days. Breakthrough bleeding and/or spotting (BTB-S) is defined as any bleeding or spotting episode that occurred during the expected non-bleeding period that was neither an early nor a continued withdrawal bleeding. Bleeding = any bloody vaginal discharge that required one or more sanitary pads or tampons per day; Spotting = any bloody vaginal discharge that required no sanitary pads or tampons per day.	Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~ 28 days)
Secondary	Percentage of Participants Who Experienced At Least One Adverse Event	An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.	Up to ~92 days
Secondary	Percentage of Participants Who Experienced At Least One Serious Adverse Event	A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose; or is another important medical event deemed such by medical or scientific judgment.	Up to ~92 days
Secondary	Percentage of Participants Who Experienced At Least One Drug-Related Adverse Event	An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. A drug-related AE was defined as any AE for which there is reasonable possibility of drug relationship as assessed by the Investigator.	Up to ~92 days
Secondary	Percentage of Participants With Any Drug-Related Serious Adverse Event	A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose; or is another important medical event deemed such by medical or scientific judgment. A drug-related SAE was defined as any SAE for which there is reasonable possibility of drug relationship as assessed by the Investigator.	Up to ~92 days
Secondary	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event	An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.	Up to ~92 days