NCT03106454

Brief Summary

Since the introduction of the combined hormonal contraceptive pill, dosages of ethinyl estradiol (EE) have steadily decreased from more than 150mcg to 20mcg in an attempt to improve the risk profile associated with the COC. In 2010, the Food and Drug Administration approved a oral contraceptive pill containing EE 10mcg/NET acetate 1mg (Tradename Lo loestrin). However, no studies have compared this formulation to pills containing either higher doses of estrogen or progestin alone. It is not known whether EE 10mcg is sufficient to prevent follicular development or to support the endometrium as well as higher doses of EE. This trial addresses the question of whether an oral contraceptive pill with EE 10mcg/Norethindrone acetate 1mg will better suppress ovulation or have a better side effect profile than a progestin only pill with a nearly equal dose of norethindrone.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Aug 2014

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2014

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

April 4, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 10, 2017

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2024

Completed
Last Updated

December 26, 2025

Status Verified

December 1, 2025

Enrollment Period

9.4 years

First QC Date

April 4, 2017

Last Update Submit

December 23, 2025

Conditions

ContraceptionOvulation

Outcome Measures

Primary Outcomes (1)

  • Ovulation

    Ovulation based on a single serum progesterone level of 4ng/dl or greater

    A single 28 day cycle

Secondary Outcomes (4)

  • Sperm penetration of cervical mucus

    A single 28 day cycle

  • Cervical mucus quality

    A single 28 day cycle

  • Side effects

    A single 28 day cycle

  • Uterine bleeding

    A single 28 day cycle

Other Outcomes (1)

  • Pill complaince

    A single 28 day cycle

Study Arms (2)

Combination oral contraceptive pill

ACTIVE COMPARATOR

Ethinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg Taken cyclically as 24 tablets containing EE 10mcg/NET acetate 1mg 2 tablets of EE 10mcg only 2 tablets of ferrous fumarate 75mg

Drug: Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate

Progestin only pill

EXPERIMENTAL

Norethindrone 0.35mg Marketed use for 1 tablet per day. For study dosing, patients will take 3 tablets daily for a total of 1.05mg daily.

Drug: Norethindrone

Interventions

Ethinyl Estradiol, Norethindrone acetate, ferrous fumarateDRUG

Combination Oral Contraceptive Pill. Ethinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg

Also known as: Loestrin
Combination oral contraceptive pill
NorethindroneDRUG

Norethindrone 1.05mg

Also known as: Micronor, Camilla
Progestin only pill

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Reproductive aged women 18-45 years old.
  • Menstrual cycle length 25-35days
  • BMI less than or equal to 40
  • English or Spanish speaking

You may not qualify if:

  • Pregnant or breastfeeding in the previous 3 months.
  • Use of OC, hormonal vaginal rings or patches, levonorgestrel containing intrauterine device, or etonogestrel implant in the previous 1 month. No use of depot medroxyprogesterone acetate (DMPA) injection in the previous 6 months and at least one menses since discontinuation.
  • Medical contraindications to estrogen or progestin use. Specifically: smoking among participants over 35 years old, migraines with aura, history of blood clots, ischemic heart disease, stroke, breast cancer, cervical cancer, liver disease, symptomatic gallbladder disease, uncontrolled hypertension, antiphospholipid antibody syndrome, hyperlipidemia, diabetes with end organ damage (retinopathy, nephropathy, neuropathy) or diagnosis \>20 years ago, organ transplant
  • Desire to become pregnant in the next 4 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brian T. Nguyen

Los Angeles, California, 90065, United States

Location

MeSH Terms

Interventions

Ethinyl EstradiolNorethindrone Acetateferrous fumaratenorethindrone acetate, ethinyl estradiol, ferrous fumarate drug combinationNorethindrone

Intervention Hierarchy (Ancestors)

NorpregnatrienesNorpregnanesNorsteroidsSteroidsFused-Ring CompoundsPolycyclic CompoundsEstrogenic Steroids, AlkylatedEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNorpregnenes

Study Officials

  • Brian T Nguyen, MD, MSc

    University of Southern California

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

April 4, 2017

First Posted

April 10, 2017

Study Start

August 1, 2014

Primary Completion

January 1, 2024

Study Completion

January 1, 2024

Last Updated

December 26, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)