AzTrials
AzTrials

ContraceptionPhase 2NCT03585712

Effect of Norgestrel 75 mcg on Cervical Mucus and Ovarian Activity During Perfect Use, After One Delayed Intake and After a Missed Pill

A Phase 2 study testing Norgestrel 0.075 mg in people with Contraception, run by HRA Pharma at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for
Contraception
What is being tested?
Norgestrel 0.075 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesUnited States
Study dates
24 Jul 2018to 7 Apr 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Oregon Health and Sciences University

    Portland, Oregon, 97239

  • University of California Davis

    Sacramento, California, 95616

Other trials in United States

About this study

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

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.

Read the 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
Conditions
Contraception
Being tested
Norgestrel 0.075 mg
Keywords
Birth Control, Progestin Only Pill, Estrogen Free Pill, Norgestrel, Oral Contraception, Female Contraception, Cervical Mucus, Ovarian Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Norgestrel 0.075 mgDrug

    Also called Norgestrel 75 mcg

    Subjects will take norgestrel 75 mcg every day at the same time for three 28-day treatment periods, except for 1 specific day during treatment period 2 and treatment period 3

Study groups in NCT03585712
Study groupRoleWhat they receive
Arm A: Delayed then Missed PillOtherTreatment period 2, Day 42 +/- 3 days: 6 hour delayed intake of Norgestrel 75 mcg Treatment period 3, Day 70 +/- 3 days: missed pill of Norgestrel 75 mcg
Receives: Drug: Norgestrel 0.075 mg
Arm B: Missed then Delayed PillOtherTreatment period 2, Day 42 +/- 3 days: missed pill of Norgestrel 75 mcg Treatment period 3, Day 70 +/- 3 days: 6 hour delayed intake of the pill of Norgestrel 75 mcg
Receives: Drug: Norgestrel 0.075 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect of Delayed Intake or Missed Pill on Cervical Mucus Score (CMS)

    Difference in Cervical Mucus Score between baseline (as Day 41 or Day 69) and delayed (Day 42 and Day 70) or missed pill (Day 43 or day 71)

    The Insler cervical mucus score (0-12) is the sum of 4 subscores:

    • viscosity from 0 (thick, highly viscous) to 3 (watery,minimally viscous)
    • ferning from 0 (no crystallization) to 3 (tertiary and quaternary stem ferning)
    • spinnbarkeit from 0 (<1 cm) to 3 (>= 9 cm)
    • rank for cells from 0 (>20 cells per High Power Field or >1000 cells per μL) to 3 (0 cell)

    A score <5 is considered as a protective score while a score >9 is considered as a non protective score

    Measured: Day 41 +/- 3 day to Day 43 +/3 days and Day 69 +/- 3 days to Day 71 +/-3 days

Secondary outcomes (5)

  1. Duration of Protective Effect of Cervical Mucus After a 6h Delayed or a Missed Pill

    Subjects are classified according to the risk of losing cervical mucus protection after a 6h delayed or a missed pill, on the day of the infringement and on the day after A cervical mucus score (CMS) <5 is considered as a protective score

    • Full protection: CMS stay <5 after both a delayed or a missed pill, on the day of infringement and on the day after.
    • Absence of risk increase: CMS stay <5 on the day of infringement and on the day after.
    • Transient risk increase: CMS increase >=5 on the day of infringement but go back to <5 on the day after.
    • Prolonged risk increase: CMS increase >=5 on the day of infringement and stay >=5 on the day after.

    Measured: Day 41 +/- 3 day to Day 43 +/3 days and Day 69 +/- 3 days to Day 71 +/-3 days

  2. Ovarian Status (OS)

    Ovarian Status (OS) defined as:

    • OSq = quiescence defined as an Ovarian Activity Score (OAS) =< 3
    • OSa = active defined as OAS = 4 or 5
    • OSalp = ovulation with abnormal luteal phase defined as OAS = 6 at only one visit
    • OSnlp = ovulation with normal luteal phase as defined as OAS = 6 at two consecutive visits or OAS = 7

    Ovarian Activity Score between 1 and 7:

    • 1= No ovarian activity
    • 2= Potential activity
    • 3= Non-active follicle like structure
    • 4= Active follicle like structure
    • 5= Postovulatory, low progesterone level
    • 6= Postovulatory, intermediate progesterone level
    • 7= Postovulatory, high progesterone level

    Measured: From Day 1 to Day 84 (if no follow-up) or up to Day 90 (if follow-up)

  3. Cervical Mucus Protection

    Higher Cervical Mucus Score (CMS) in:

    • Treatment Period 1 (Reported Perfect Use Period)
    • Delayed pill period: Treatment Period 2 for Arm A and Treatment Period 3 for Arm B
    • Missed pill period: Treatment Period 3 for Arm A and Treatment Period 2 for Arm B

    A score =< 4 is considered as a protective score and a score >= 9 is considered as a non protective score

    Measured: From Day 1 to Day 84

  4. Conception Protection Risk

    Binary analysis of whether a subject is at risk of conception based only on their ovarian status (OS) and cervical mucus score (CMS) the days before ovulation:

    Are considered protected, subjects with OSq, OSa OR CMS =<4 Are considered at risk, subjects with OSalp or OSnlp AND CMS >=5

    Measured: Day 1 to Day 84 (up to Day 90 if follow-up)

  5. Conception Protection Level

    Ternary analysis of the level of protection from conception of subjects, based only on the ovarian status (OS) and cervical mucus score (CMS) the days before ovulation:

    • Minimum protection or unlikely to be protected: OSnlp and CMS ≥ 9
    • Medium protection or likely to be protected: OSnlp and CMS comprised between 5 and 8 or OSalp and CMS ≥ 5
    • Maximum protection or highly likely to be protected: OSq or OSa or a CMS ≤ 4

    Measured: Day 1 to Day 84 (up to Day 90 if follow-up)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2018
  2. Study start24 Jul 2018
  3. Primary completion7 Apr 2020
  4. Study completion7 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03585712
Sponsor's protocol ID
151042-002
Status last verified
Jun 2021
First submitted
5 Jul 2018
Last updated
3 Jun 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33970869

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Norgestrel 0.075 mg in people with Contraception, run by HRA Pharma at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Delayed Intake or Missed Pill on Cervical Mucus Score (CMS) (time frame: Day 41 +/- 3 day to Day 43 +/3 days and Day 69 +/- 3 days to Day 71 +/-3 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03585712, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in