Oral Levonorgestrel Plus Meloxicam, IG-002 Delays Ovulation in Normal Menstruating Women by Seven Days

NCT05695352 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IG-20-001 V2.01R43HD104508-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial determines if an oral medication taken within 2 days of anticipated ovulation will delay ovulation by 7 days. The study compares oral placebo tablets (control) to oral levonorgestrel, a synthetic hormone, and meloxicam, a non-steroidal anti-inflammatory drug (treatment) in 21 healthy women between the ages of 18 to 40. The control or treatment are taken 48 hours apart in the first and second menstrual cycle, respectively. The first dose is taken when the ovarian follicle has a diameter of 17 mm measured by transvaginal ultrasound. This follicle diameter is found 2 ± 1.0 days before ovulation. Ovulation is determined by a change in urinary hormone levels analyzed in first morning daily urine. The Investigators anticipate that the control cycle will have an interval to ovulation of ≤ 3 days from first placebo to ovulation while a delay of ≥7 days is found between first treatment to ovulation. A second question is to determine the side effects between control versus treatment based on symptoms such as nausea or abdominal cramping, change in blood pressure or pulse rate and the interval in menstrual bleeding. Each study participant has approximately 9 visits during each of two menstrual cycles. The visits between menstrual day 9 (first visit) to largest follicle are 3 to 6 depending upon follicle growth. A blood sample with a transvaginal ultrasound for ovarian follicle diameter is obtained at each visit. The appropriate medication is taken when the ovarian follicle largest diameter is 17 mm. The second dose is taken 2 days later with interim and final visits at 5 and 10 days following first dose. Each participant collects first morning urine from menstrual day 9 to 23. A teaspoonful of morning urine is placed in a storage tube and kept in a refrigerator freezer section until returned at a scheduled visit. All urine samples are kept frozen until analyzed for the metabolites of estrogen and progesterone by a central research laboratory. A change in the ratio of estrogen to progesterone metabolites is indicative of ovulation because more progesterone is secreted after ovulation from the ovary. The primary research outcome compares the interval in days from first dose of medication to ovulation between control and treatment. Secondary outcomes are menstrual cramps, vaginal bleeding, nausea, and headache, and changes in blood pressure, pulse, and interval between menstrual periods in control compared to treatment cycles.

Conditions

Pregnancy Prevention

Keywords

Female; Hormonal Contraception; Emergency contraception; levonorgestrel; Meloxicam

Outcome Measures

Primary Outcomes (1)

• Interval to Ovulation in Normal Women Following Placebo is Anticipated to be Three Days Compared to Seven Days Following Levonorgestrel Plus Meloxicam

  The participant will take the first dose of medication (either placebo or intervention) when an ovarian follicle measuring at least 17 mm in diameter is found on transvaginal ultrasound and a second dose 48 hours later. Daily morning urine samples were analyzed for pregnanediol-3-glucuronide (PDG) and creatinine. A 100% increase in urinary PDG levels was used to indicate day of ovulation, also known as the follicular luteal shift. The interval from first dose of placebo to follicular luteal shift is estimated to be three days. The active treatment will be given the same way during the subsequent second cycle when the ovarian follicle diameter is also at least 17 mm. The intervention outcome is estimated to be a delay of seven or more days from first dose to the follicular luteal shift or ovulation.

  The outcome will be assessed at the end of the first and second menstrual cycle of 28 ± 2.0 Days, respectively in up to two menstrual cycles.

Secondary Outcomes (1)

• Safety Using Blood Pressure, Specifically Systolic Blood Pressure

  Changes in the mean sitting systolic blood pressure during the placebo and intervention menstrual cycles. For each cycle, sitting blood pressures were measured on the following days: first dose, second dose and ten days from first dose.

Other Outcomes (3)

• Menstrual Bleeding Interval for Both the Placebo and Intervention Cycle.

  Menstrual interval for both placebo and intervention cycles; from menstrual day 1 to end of cycle in placebo compared to intervention cycle with each cycle approximately 28 ± 2.0 days. Measurements are made in up to two menstrual cycles.

• Unscheduled Vaginal Bleeding

  All incidences of unscheduled bleeding within the placebo and intervention cycles were collected, with each cycle approximately 28 ± 2.0 days.

• Report the Number of Participants Who Reported Adverse Events in Both the Placebo and Intervention Arms

  Events are measured from day one to end of cycle in placebo cycle compared to day one to end of cycle in the intervention cycle with each cycle anticipated to be 28 ± 2.0 days. Adverse events are collected for two menstrual cycles.

Study Arms (1)

Placebo comparator in first menstrual cycle and Intervention in the second menstrual cycle

EXPERIMENTAL

The two arm placebo comparator study will use each participant as her own control with a placebo arm in the first menstrual cycle consisting of two placebo tablets taken at the time of the ovarian follicle measuring 17 mm in diameter and a second dose of two tablets 48 hours later. During the subsequent second menstrual cycle the participant will take the intervention, one tablet of levonorgestrel 1.5 mg and one tablet of meloxicam 15 mg, at the time of the ovarian follicle measures at least 17 mm in diameter and a second dose of the two tablets intervention 48 hours later.

Drug: Levonorgestrel 1.5mg; Drug: Meloxicam 15 mg; Other: Placebo

Interventions

Levonorgestrel 1.5mg DRUG

oral synthetic progesterone agonist

Also known as: Plan B one step

Placebo comparator in first menstrual cycle and Intervention in the second menstrual cycle

Meloxicam 15 mg DRUG

Non steroidal autoinflammatory drug inhibiting both Cyclooxygenase -1 and -2 enzymes

Also known as: Mobic

Placebo comparator in first menstrual cycle and Intervention in the second menstrual cycle

Placebo OTHER

Each tablet contains Calcium Carbonate 1000 mg

Also known as: TUMS

Placebo comparator in first menstrual cycle and Intervention in the second menstrual cycle

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Female with normal ovarian function
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Female in good general health with no chronic medical conditions that result in periodic exacerbations that require significant medical care.
• \. Age between 18 to 40 years inclusive at time of enrollment. 3. BMI ≤30 kg/m² and no recent rapid weight loss or gain. 4. Intact uterus with both ovaries intact. 5. PAP test within ASCCP or ACOG guidelines such that additional testing or evaluation will not be required during the study period. If there is no copy of a recent PAP test and the subject is 21 years or older a Pap test should be done during the screening visit.
• \. Regular menstrual cycles with an interval of 24 to 32 days:
• If postpartum of post-second trimester abortion, she must have 5 menses prior to enrollment.
• If the subject has had a first trimester pregnancy loss or abortion, she must have one spontaneous menses prior to enrollment.
• \. Have a negative urine pregnancy test on menstrual cycle day 9 pre-treatment visit.
• \. Not at risk of pregnancy for the duration of the study defined as heterosexually abstinent, prior female or male permanent contraception, non-hormonal intrauterine device or willing to use a non-hormonal barrier contraceptive method with each act of intercourse until study exit.
• \. Subject is willing and able in the Investigators opinion of complying with protocol requirement's 10. Subject is willing to collect daily urine first morning urine and store them until collected.
• \. Lives within the study catchment area or a reasonable distance from the study site.
• \. Understands and signs the IRB approved informed consents prior to undergoing any screening assessment.
• \. Agrees not to participate in any other clinical trials during the course of this study.
• \. Screening serum progesterone level greater than 3 ng/ml.

You may not qualify if:

• Known hypersensitivity or contraindications to progestins.
• Abnormal transvaginal ultrasound or safety laboratory results evaluated during the screening period recognized as clinically significant aby the investigator or medically qualified designee.
• Known or suspected alcohol or marijuana abuse.
• Undiagnosed abnormal genital bleeding.
• Undiagnosed vaginal discharge, lesions or abnormalities. Women with a history of genital herpes can be included if the outbreaks are infrequent. Antiviral prophylaxis is allowed.
• Uncontrolled Thyroid disorder.
• Current use of hormonal contraception or a levonorgestrel releasing intrauterine device.
• Use of a long-acting injectable hormonal contraceptive within the past 6 months unless has had at least one spontaneous menstrual cycle (two menstrual bleeding episodes) since the last injection.
• Breastfeeding women or those who have not had a spontaneous menstrual bleed since discontinuing breastfeeding.
• Women who plan a major surgical procedure during the study.
• Women who plan to become pregnant during their participation in the study.
• Women who smoke \>15 cigarettes per day or who use \>1 mL/day of nicotine-containing liquid for electronic cigarettes.
• Current or history of ischemic heart disease or stroke while pregnant or during use of hormonal contraception.
• Current or past deep vein thrombosis or thromboembolic disorder.
• Personal or family history of thrombophilia

Sponsors & Collaborators

• InnovaGyn, Inc.: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Carolina Women's Research and Wellness Center

Raleigh, North Carolina, 27713, United States

Location

Related Publications (25)

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MeSH Terms

Interventions

Levonorgestrel; Meloxicam

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Thiazines; Sulfur Compounds; Organic Chemicals; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

We needed 22 women to complete the study in order to show that the intervention significantly delayed ovulation compared to placebo. Only 19 women were enrolled with two women being dropped from the analysis, one did not do the intervention arm, and one was anovulatory in both cycles. There were significant problems with recruiting despite numerous attempts by the clinical site with participants mentioning that the number of visits and proximity of each visit made it difficult to schedule.

Results Point of Contact

• Title: David F. Archer, MD, Chief Executive Officer
• Organization: InnovaGyn, Inc.

darcher@innovagyn.co

(757) 434-5864

Study Officials

• David F. Archer, MD

  InnovaGyn, Inc.

  PRINCIPAL INVESTIGATOR

• William L. McPheat, PhD

  InnovaGyn, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This open label study will be masked by not allowing the analysis of the urine samples collected for determining the day of the follicular luteal transition (ovulation) to be known to the laboratory director and technicians.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Executive Officer

Model Details: The study design is an open label randomized single blind clinical trial in which each participant will receive placebo two tablets 48 hours apart in their first menstrual cycle and then levonorgestrel plus meloxicam 48 hours apart in their subsequent menstrual cycle. We will compare the interval from taking the first dose of medication to the development of a functioning corpus luteum based on the shift in the ratio of urinary estrone-3-glucuronide(EC) / pregnanediol-3-glucuronide (PDG). An "n" of 21 was calculated using the Log-Rank Test method and setting the Power to 80% and alpha to 0.05 to test the hypothesis that there was no difference between the "survival curves" for the placebo and drug-treated cycles.

Study Record Dates

• First Submitted: January 2, 2023
• First Posted: January 25, 2023
• Study Start: June 28, 2022
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2025
• Last Updated: June 17, 2026
• Results First Posted: June 17, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon completion of the study and with acceptance of the outcome manuscript by a professional journal.
• Access Criteria: The Access Criteria to be shared are: 1. Differences in the interval from first dose of placebo or treatment to ovulation. This interval is the primary outcome. 2. All treatment emergent adverse events. 3. The menstrual bleeding interval and unscheduled bleeding. 4. Blood pressure and pulse between treatments

Locations

US (1)