Clinical trial NCT03585712: Effect of Norgestrel 75 mcg on Cervical Mucus and Ovarian Activity During Perfect Use, After One Delayed Intake and After a Missed Pill
Official title: A Prospective, Multi-center, Randomized, Cross-over Study to Assess the Effect of Norgestrel 75 mcg on Cervical Mucus and Ovarian Activity During Perfect Use, After One Delayed Intake and After a Missed Pill
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Contraception
Keywords: Birth Control
Progestin Only Pill
Estrogen Free Pill
Norgestrel
Oral Contraception
Female Contraception
Cervical Mucus
Ovarian Activity
Lead sponsor: HRA Pharma
Sponsor class: INDUSTRY
Collaborators: name: Health Decisions
First posted: 2018-07-13
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Norgestrel 75 mcg is a progestin-only pill (POP), which is a kind of oral birth control pill.

To be effective in preventing pregnancy, this kind of birth control pill is supposed to be taken every day at the same time, without delaying the intake for more than 3 hours.

This study aims to find out if taking the pill 6 hours late or not taking it for one day will affect the way it works.

Detailed description: This study is an exploratory, prospective, multi-center, randomized, cross-over study to assess the effect of norgestrel 75 mcg on cervical mucus and ovarian activity during reported perfect daily use, after a delayed intake of 6 hours and after a missed pill.

After a screening period up to one month, depending on the menstrual cycle of the subject, the subjects will take norgestrel 75 mcg for three 28-day treatment periods, every day at the same time except for one day in the middle of treatment period 2 and treatment period 3 where they will either take it 6 hours late or not take it.

In week 5 (1st visit of treatment period 2), they will be randomized to 2 sequences, either 6 hours delayed intake in treatment period 2 and missed pill in treatment period 3 or the opposite.

After the end of treatment period 3, a follow-up up to 12 days may be required to follow ovarian activities.

Subjects will have visits twice a week and sometimes more often to assess the effects of the pill on:

* cervical mucus properties by a cervical mucus sampling
* ovarian activity by a vaginal ultrasound (TVUS)
* reproductive hormones levels by a blood sample (Progesterone (P4), Estradiol (E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH))
* plasma drug level by a blood sample

Eligibility criteria: Inclusion Criteria:

* Women in good overall health with no chronic medical conditions that result in periodic exacerbations that require significant medical care
* Women between 18 and 35 years inclusive at the screening visit
* BMI\< 32 kg/m²
* Regular menstrual cycles between 21 and 35 days when not using hormonal contraception.

  * Subjects postpartum or post-abortal must have one normal menstrual cycle (2 menses) prior to enrollment.
  * Subjects previously using Intra-Uterine Device (IUD) or taking hormonal contraception (or any other hormonal treatment, except an injectable treatment) need to have at least one menstrual cycle (2 menses) without the treatment before screening.
  * Subject previously using an injectable (DMPA), must have had their last injection at least 9 months before screening.
* Women not at risk of pregnancy: not sexually active, or willing to protect all acts of intercourse with condoms, or have a sterile partner or have undergone previous tubal ligation (including validated Essure), or be in a same sex relationship.
* Women able to give informed consent form to participate in the study and in the opinion of the investigator able to follow all study requirements, use the study medication and record the requested information appropriately
* Intact uterus and both ovaries
* At least one progesterone concentration \> 3 ng/mL (\>10 nmol/L) during the luteal phase of the screening period

Exclusion Criteria:

* Pregnant as confirmed by positive high-sensitivity urine pregnancy test at enrollment visit
* Trying to conceive or desire to conceive in the next 3 months
* Currently breastfeeding, or within the last 2 months
* Known Polycystic Ovarian Syndrome (PCOS)
* Cancer (or past history of any carcinoma or sarcoma)
* Known abnormal thyroid status, if in clinical judgment of the investigator it cannot be controlled during the study
* Known hypersensitivity to the ingredients of the test active substances or its excipients
* Current acute liver disease and/or benign liver tumors
* Have vaginal or cervical infection including clinical evidence of bacterial vaginosis
* Evidence of abnormal cervical lesion
* History of excisional or ablative treatment procedure on cervix (ie. Loop Electrosurgical Excision Procedure (LEEP), Cryotherapy, Cold Knife Cone)
* Undiagnosed abnormal uterine bleeding
* Prior malabsorptive-type bariatric surgery
* Known or suspected alcoholism or illicit drug abuse
* Use of any hormonal contraception or IUD other than the study medication during the study (including ulipristal acetate for emergency contraception in the past 5 days)
* Use of any medications that can interfere with the metabolism of progestin-based contraceptives (e.g CYP3A4 enzymes inducers or inhibitors, etc)
* Unstable diabetes mellitus
* Current participation in any other trial of an investigational medicine or participation in the past two months (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for antibodies, whichever is the longer) before screening
* Abnormalities in laboratory results or TVUS performed at screening visit recognized as clinically significant by the investigator
* Conditions not suitable for frequent TVUS examinations, (e.g. virgo intacta)
* In custody or submitted to an institution due to a judicial order
* Relative or household member of the investigator's or sponsor's staff

Primary outcomes:
measure: Effect of Delayed Intake or Missed Pill on Cervical Mucus Score (CMS)
timeFrame: Day 41 +/- 3 day to Day 43 +/3 days and Day 69 +/- 3 days to Day 71 +/-3 days
Secondary outcomes:
measure: Duration of Protective Effect of Cervical Mucus After a 6h Delayed or a Missed Pill
timeFrame: Day 41 +/- 3 day to Day 43 +/3 days and Day 69 +/- 3 days to Day 71 +/-3 days
measure: Ovarian Status (OS)
timeFrame: From Day 1 to Day 84 (if no follow-up) or up to Day 90 (if follow-up)
measure: Cervical Mucus Protection
timeFrame: From Day 1 to Day 84
measure: Conception Protection Risk
timeFrame: Day 1 to Day 84 (up to Day 90 if follow-up)
measure: Conception Protection Level
timeFrame: Day 1 to Day 84 (up to Day 90 if follow-up)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
Study officials:
affiliation: Oregon Health and Sciences University
name: Alison Edelman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Mitchell Creinin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edelman A, Hemon A, Creinin M, Borensztein P, Scherrer B, Glasier A. Assessing the Pregnancy Protective Impact of Scheduled Nonadherence to a Novel Progestin-Only Pill: Protocol for a Prospective, Multicenter, Randomized, Crossover Study. JMIR Res Protoc. 2021 Jun 8;10(6):e29208. doi: 10.2196/29208.