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

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.

Time frame: Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~28 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and had an evaluable cycle with non-missing bleeding data in the respective cycle, excluding participants who were protocol violators in terms of ring use, daily diary entry or prohibited medications.

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).

Time frame: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and received ultrasound and hormonal assessments, excluding participants who were protocol violators in terms of ring use, daily diary entry or prohibited medications.

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.

Time frame: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and received hormonal assessment for progesterone concentration, excluding participants who were protocol violators in terms of ring use, daily diary entry or prohibited medications.

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.

Time frame: Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~ 28 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and had an evaluable cycle with non-missing bleeding data in the respective cycle, and with at least one breakthrough bleeding and/or spotting day, excluding protocol violators in terms of ring use, daily diary entry or prohibited medications.

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.

Time frame: Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and had an evaluable cycle with non-missing bleeding data in the respective cycle, and with at least one withdrawal bleeding or spotting day, excluding participants who were protocol violators in terms of ring use, daily diary entry or prohibited medications.

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.

Time frame: Up to ~92 days

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.

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.

Time frame: Up to ~92 days

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.

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.

Time frame: Up to ~92 days

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.

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.

Time frame: Up to ~92 days

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.

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.

Time frame: Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)

Population: The analysis population included all participants in whom vaginal rings were inserted and had an evaluable cycle with non-missing bleeding data in the respective cycle, excluding participants who were protocol violators in terms of ring use, daily diary entry or prohibited medications.

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.

Time frame: Up to ~92 days

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.

Venous or arterial thrombotic/thrombo-embolic events, (VTEs or ATEs) (e.g., deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident) were assessed.

Time frame: From Cycle 1 Day 1 up to 8 days after Day 28 of Cycle 3 (Up to ~92 days)

Population: The analysis population included all randomized participants in whom a vaginal ring was inserted.