Phase II Study of Ovulation in Obese Women

NCT06306131 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IG-23-0021R43HD107861-01A1
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the delay in ovulation between placebo to levonorgestrel plus meloxicam in obese women with normal menses. The main questions it aims to answer are:

• undergo two treatment cycles the 1st uses placebo and the 2nd is levonorgestrel plus meloxicam,
• maintain daily diary logs for adverse events, unscheduled bleeding, and onset, cessation, and amount of menstrual bleeding,
• collect daily first morning voided urine from menstrual day 9 to 24,
• undergo transvaginal ultrasound for ovarian follicle development on menstrual days 9, 11,13 and 14.
• allow a blood sample to be drawn on days with ultrasound scans.
• Take 1st placebo and levonorgestrel plus meloxicam under observation when dominant ovarian follicle is 17 ±1.0 millimeters (mm) in diameter and 2nd dose 48 hours later. Researchers will compare the placebo cycle to levonorgestrel plus meloxicam to see if ovulation is delayed, there is unscheduled vaginal bleeding, menstrual onset is delayed or there is an abnormal amount or duration of menses, there is any difference in treatment emergent side effects and any change in vital signs

Conditions

Pregnancy Prevention

Keywords

Female; Hormonal contraception; Emergency Contraception; levonorgestrel; meloxicam

Outcome Measures

Primary Outcomes (1)

• Interval From First Dose to Evidence of Ovulation.

  An ovarian follicle diameter of 17 mm is used to take the first dose of medication. 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, the follicular luteal shift. The interval from first dose of placebo (calcium carbonate) to follicular luteal shift is estimated to be 3 days. The active treatment (levonorgestrel 1.5 mg and meloxicam 15 mg) will be given the following month when the ovarian follicle diameter is also 17 mm. The outcome is estimated to be a delay of 7 + days from 1st dose to the follicular luteal shift or ovulation with the active treatment. Urinary PDG values were assessed to 10 days from first dose of both placebo and active treatment.

  The interval is estimated to be 3 days from first dose of placebo to evidence of ovulation, and the interval is estimated to be 7 days from first dose of intervention to evidence of ovulation. Assessment was to 10 days from first dose.

Secondary Outcomes (2)

• Change in Pulse Rate. The Measured Pulse Rate From the Day of the First Dose Minus the Pulse Rate Measured 10 Days From the First Dose.

  Pulse rate is measured at all clinic visits during each menstrual cycle but only the day of first dose and 10 days from first dose was used for this outcome measure.

• Change in Blood Pressure. The Measured Blood Pressure From the Day of the First Dose Minus the Blood Pressure Measured 10 Days From the First Dose.

  Blood pressure is measured at all clinic visits during each menstrual cycle but only the day of first dose and 10 days from first dose was used for this outcome measure.

Other Outcomes (2)

• Unscheduled Vaginal Bleeding

  The participants will report on daily diary cards any bleeding from menstrual day 9 of the first cycle to the exit visit which is within two weeks of the final (third) menstrual period, an assessed time period up to 90 days.

• Menstrual Cycle Interval

  Menstrual cycle intervals will be determined from Day 1 to Day 45 in both cycles, assessed up to a total of 90 days.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The placebo is calcium carbonate 750 milligram (mg) known as TUMS. Each participant will take one tablet orally and repeat 48 hours later.

Other: calcium carbonate 750 milligram

Levonorgestrel plus meloxicam

ACTIVE COMPARATOR

The active comparator is levonorgestrel 1.5 milligram (mg) and meloxicam 15 milligram (mg) taken together orally and repeated 48 hours later.

Drug: Levonorgestrel 1.5 milligram; Drug: Meloxicam 15 milligram

Interventions

Meloxicam 15 milligram DRUG

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).

Also known as: Mobic

Levonorgestrel plus meloxicam

calcium carbonate 750 milligram OTHER

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).

Also known as: TUMS

Placebo

Levonorgestrel 1.5 milligram DRUG

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).

Also known as: Plan B one Step

Levonorgestrel plus meloxicam

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Designated as female at birth.
• 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.
• BMI ≥30 kg/m² and no recent rapid weight loss or gain.
• Intact uterus with both ovaries intact.
• Papanicolaou test within American Society for Colposcopy and Cervical Pathology (ASCCP), or American College of Obstetricians and Gynecologists (ACOG) guidelines such that additional testing or evaluation will not be required during the study period. If there is no copy of a recent Papanicolaou test and the subject is 21 years or older a Papanicolaou test should be done during the screening visit.
• Regular menstrual cycles with an interval of 24 to 32 days:
• If postpartum or post-second trimester abortion, she must have 2 spontaneous 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 requirements.
• Subject is willing to collect daily first morning urines and store them until brought to the study site.
• Lives within the study catchment area or a reasonable distance from the study site.
• Understands and signs the IRB approved informed consent prior to undergoing any screening assessment.
• Agrees not to participate in any other clinical trials during the course of this study.

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 by 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.

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 (23)

• Raymond EG, Shochet T, Drake JK, Westley E. What some women want? On-demand oral contraception. Contraception. 2014 Aug;90(2):105-10. doi: 10.1016/j.contraception.2014.04.008. Epub 2014 Apr 21.

  PMID: 24835831 BACKGROUND

• Daniels K, Mosher WD. Contraceptive methods women have ever used: United States, 1982-2010. Natl Health Stat Report. 2013 Feb 14;(62):1-15.

  PMID: 24988816 BACKGROUND

• Moreau C, Cleland K, Trussell J. Contraceptive discontinuation attributed to method dissatisfaction in the United States. Contraception. 2007 Oct;76(4):267-72. doi: 10.1016/j.contraception.2007.06.008. Epub 2007 Aug 28.

  PMID: 17900435 BACKGROUND

• Trussell J. Contraceptive failure in the United States. Contraception. 2004 Aug;70(2):89-96. doi: 10.1016/j.contraception.2004.03.009.

  PMID: 15288211 BACKGROUND

• Simmons RG, Sanders JN, Geist C, Gawron L, Myers K, Turok DK. Predictors of contraceptive switching and discontinuation within the first 6 months of use among Highly Effective Reversible Contraceptive Initiative Salt Lake study participants. Am J Obstet Gynecol. 2019 Apr;220(4):376.e1-376.e12. doi: 10.1016/j.ajog.2018.12.022. Epub 2018 Dec 18.

  PMID: 30576664 BACKGROUND

• Venners SA, Liu X, Perry MJ, Korrick SA, Li Z, Yang F, Yang J, Lasley BL, Xu X, Wang X. Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy. Hum Reprod. 2006 Sep;21(9):2272-80. doi: 10.1093/humrep/del187. Epub 2006 Jun 23.

  PMID: 16798842 BACKGROUND

• Bradley SEK, Polis CB, Bankole A, Croft T. Global Contraceptive Failure Rates: Who Is Most at Risk? Stud Fam Plann. 2019 Mar;50(1):3-24. doi: 10.1111/sifp.12085. Epub 2019 Feb 21.

  PMID: 30791104 BACKGROUND

• Pace LE, Dusetzina SB, Keating NL. Early Impact Of The Affordable Care Act On Oral Contraceptive Cost Sharing, Discontinuation, And Nonadherence. Health Aff (Millwood). 2016 Sep 1;35(9):1616-24. doi: 10.1377/hlthaff.2015.1624.

  PMID: 27605641 BACKGROUND

• Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE. Ovulation: Parallels With Inflammatory Processes. Endocr Rev. 2019 Apr 1;40(2):369-416. doi: 10.1210/er.2018-00075.

  PMID: 30496379 BACKGROUND

• Croxatto HB, Brache V, Pavez M, Cochon L, Forcelledo ML, Alvarez F, Massai R, Faundes A, Salvatierra AM. Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation. Contraception. 2004 Dec;70(6):442-50. doi: 10.1016/j.contraception.2004.05.007.

  PMID: 15541405 BACKGROUND

• Devoto L, Fuentes A, Palomino A, Espinoza A, Kohen P, Ranta S, von Hertzen H. Pharmacokinetics and endometrial tissue levels of levonorgestrel after administration of a single 1.5-mg dose by the oral and vaginal route. Fertil Steril. 2005 Jul;84(1):46-51. doi: 10.1016/j.fertnstert.2005.01.106.

  PMID: 16009156 BACKGROUND

• Brache V, Cochon L, Deniaud M, Croxatto HB. Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens. Contraception. 2013 Nov;88(5):611-8. doi: 10.1016/j.contraception.2013.05.010. Epub 2013 May 22.

  PMID: 23809278 BACKGROUND

• Duffy DM. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway. Hum Reprod Update. 2015 Sep-Oct;21(5):652-70. doi: 10.1093/humupd/dmv026. Epub 2015 May 29.

  PMID: 26025453 BACKGROUND

• Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, Gainer E, Ulmann A. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011 Oct;84(4):363-7. doi: 10.1016/j.contraception.2011.02.009. Epub 2011 Apr 2.

  PMID: 21920190 BACKGROUND

• Glasier A. Emergency contraception: clinical outcomes. Contraception. 2013 Mar;87(3):309-13. doi: 10.1016/j.contraception.2012.08.027. Epub 2012 Oct 4.

  PMID: 23040128 BACKGROUND

• Festin MP, Bahamondes L, Nguyen TM, Habib N, Thamkhantho M, Singh K, Gosavi A, Bartfai G, Bito T, Bahamondes MV, Kapp N. A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg. Hum Reprod. 2016 Mar;31(3):530-40. doi: 10.1093/humrep/dev341. Epub 2016 Jan 31.

  PMID: 26830816 BACKGROUND

• Trussell J. Contraceptive failure in the United States. Contraception. 2011 May;83(5):397-404. doi: 10.1016/j.contraception.2011.01.021. Epub 2011 Mar 12.

  PMID: 21477680 BACKGROUND

• Jesam C, Salvatierra AM, Schwartz JL, Croxatto HB. Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception. Hum Reprod. 2010 Feb;25(2):368-73. doi: 10.1093/humrep/dep392. Epub 2009 Nov 19.

  PMID: 19933235 BACKGROUND

• Bata MS, Al-Ramahi M, Salhab AS, Gharaibeh MN, Schwartz J. Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study. J Clin Pharmacol. 2006 Aug;46(8):925-32. doi: 10.1177/0091270006289483.

  PMID: 16855077 BACKGROUND

• Massai MR, Forcelledo ML, Brache V, Tejada AS, Salvatierra AM, Reyes MV, Alvarez F, Faundes A, Croxatto HB. Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study. Hum Reprod. 2007 Feb;22(2):434-9. doi: 10.1093/humrep/del369. Epub 2006 Sep 15.

  PMID: 16980507 BACKGROUND

• Santoro N, Crawford SL, Allsworth JE, Gold EB, Greendale GA, Korenman S, Lasley BL, McConnell D, McGaffigan P, Midgely R, Schocken M, Sowers M, Weiss G. Assessing menstrual cycles with urinary hormone assays. Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E521-30. doi: 10.1152/ajpendo.00381.2002. Epub 2002 Nov 19.

  PMID: 12441312 BACKGROUND

• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.

  PMID: 18929686 BACKGROUND

• Gemzell-Danielsson K, Berger C, P G L L. Emergency contraception -- mechanisms of action. Contraception. 2013 Mar;87(3):300-8. doi: 10.1016/j.contraception.2012.08.021. Epub 2012 Oct 29.

  PMID: 23114735 RESULT

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

Due to limited number of participants, this study cannot adequately assess whether a delay in ovulation occurred with the intervention arm, levonorgestrel 1.5 mg and meloxicam 15 mg, compared to the placebo, calcium carbonate 750 mg. Multiple attempts were made by the clinical site to increase enrollment, and they reported that potential participants commented that the number of visits and the proximity of each visit made involvement difficult.

Results Point of Contact

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

darcher@innovagyn.co

(757) 434-5864

Study Officials

• Andrea Lukes, MD

  Carolina Woman's Research and Wellness Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The intervention will be masked to the laboratory preforming the analysis of the urinary metabolites. The statistician, clinicians, coordinators and participants will be aware of the medication being studied.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo controlled in first cycle with levonorgestrel plus meloxicam in second menstrual cycle.

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: March 12, 2024
• Study Start: December 10, 2023
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: June 30, 2026
• Results First Posted: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)