A Study to Evaluate the PK and PD of IM or SQ Injections of Levonorgestrel Butanoate (LB) for Female Contraception

NCT04143659 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CCN021
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Phase I multicenter, open-label, dose-ranging, three-dose PK and PD study of injectable LB administered as an IM or SQ injection at 40 mg, and subsequently at 50mg SQ and then 60 mg SQ depending on the preliminary pharmacokinetic and pharmacodynamic results obtained with 40 mg dosing.

Conditions

Healthy Women; Female Contraception

Outcome Measures

Primary Outcomes (1)

• Measurement of levonorgestrel serum concentrations

  0, 2, 4, 6, 8, 24, 48, 96, 168, and 240 hours. Then weekly for up to 26 weeks.

Secondary Outcomes (7)

• Ultrasound measurements of ovarian follicular development and ovulation including follicle diameter, total number of follicles, and the number of follicles exceeding a pre-specified threshold

  Weekly up to 26 weeks

• Measurement of Endometrial thickness

  Weekly up to 26 weeks

• Steroid hormone (Estradiol) concentration

  Weekly up to 26 weeks

• Gonadotropin (Follicle Stimulating Hormone and Luteinizing Hormone) concentrations

  Weekly up to 26 weeks

• Sex Hormone Binding Globulin (SHGB) concentration

  Weekly up to 26 weeks

Study Arms (5)

LB injection 40mg intramuscular (IM) with 20 mg/ml concentration

EXPERIMENTAL

27 subjects (18 with BMI \<30mg\^2; 9 with BMI \>=30kg/m\^2 and \<40kg/m\^2) were administered a single dose of levonorgestrel butanoate (LB) injection 40mg intramuscular (IM) using 20 mg/ml concentration

Biological: levonorgestrel butanoate (LB) injection

LB injection 40 mg subcutaneous (SC) with 20 mg/ml concentration

EXPERIMENTAL

32 subjects (25 with BMI \<30mg\^2; 7 with BMI \>=30kg/m\^2 and \<40kg/m\^2) were administered a single dose of levonorgestrel butanoate (LB) injection 40mg subcutaneous (SC) using 20 mg/ml concentration

Biological: levonorgestrel butanoate (LB) injection

LB injection 50mg subcutaneous (SQ) with 70 mg/ml concentration

EXPERIMENTAL

8 subjects (8 with BMI \<40 kg/m2) will be administered a single dose of levonorgestrel butanoate (LB) injection 50mg intramuscular (IM) using 70 mg/ml concentration

LB injection 60mg Subcutaneous (SQ) with 70 mg/ml concentration

EXPERIMENTAL

32 subjects (16 with BMI \<30mg\^2; 16 with BMI \>=30kg/m\^2 and \<40kg/m\^2) will be administered a single dose of levonorgestrel butanoate (LB) injection 60mg subcutaneous (SC) using 70 mg/ml concentration

LB injection 40 mg subcutaneous (SQ) with 70 mg/ml concentration

EXPERIMENTAL

32 subjects (21 with BMI \<30mg\^2; 11 with BMI \>=30kg/m\^2 and \<40kg/m\^2) were administered a single dose of levonorgestrel butanoate (LB) injection 40mg subcutaneous (SC) using 70 mg/ml concentration

Biological: levonorgestrel butanoate (LB) injection

Interventions

levonorgestrel butanoate (LB) injection BIOLOGICAL

The initial formulation of the investigational product (IP) is LB Injectable Suspension at a concentration of 40 mg/2 mL (20 mg/mL). Each vial contains 2 mL at 20mg/mL for a total of 40 mg. This formulation will only be used for dosing groups A and B with the injections completed as 40 mg IM (2 mL) or 40 mg SQ (2 mL). The second formulation of the investigational product (IP) is LB Injectable Suspension is a concentration of 140 mg/2 mL (70 mg/mL). Each vial contains 2 mL at 70 mg/mL for a total of 140 mg. This formulation will only be used for dosing groups B2, C, and D with the injections completed as 40 mg SQ (0.57 mL), 50 mg SQ (0.71 mL), and 60 mg SQ (0.86 mL).

LB injection 40 mg subcutaneous (SC) with 20 mg/ml concentration; LB injection 40 mg subcutaneous (SQ) with 70 mg/ml concentration; LB injection 40mg intramuscular (IM) with 20 mg/ml concentration

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Good general health with no chronic medical conditions that result in periodic exacerbations that require significant medical care.
• Age between 18 and 40 years inclusive at the injection visit.
• BMI \< 40 kg/m2.
• Intact uterus with at least one ovary.
• Pap test within ASCCP or ACOG guidelines such that additional treatment will not be required during the study period. If a copy of a Pap test (and indicated follow-up testing) is not available and the subject is 21 years or older, a Pap test should be done during the screening period.
• Regular menstrual cycles that occur every 21-35 days:
• a. If subject is postpartum or post-second trimester abortion, she must have 3 menses (2 cycles) prior to enrollment.
• b. If subject had a first trimester abortion or pregnancy loss, she must have one spontaneous menses prior to enrollment.
• \. Have a negative urine pregnancy test at the injection visit and no unprotected heterosexual intercourse for the previous 10 days.
• \. Not at risk for pregnancy for the duration of study participation (screening through last phone contact), defined as one of the following: 8a. heterosexually abstinent; 8b. previous female permanent contraception procedure; 8c. in a monogamous relationship with a vasectomized partner; 8d. consistent use of a non-hormonal barrier method with every act of intercourse (e.g. condoms or diaphragm + spermicide).
• e. use copper IUD 9. Subjects must be ovulatory as confirmed by a documented screening progesterone (P4) level ≥ 3 ng/ml by local laboratory.
• \. In the opinion of the investigator, subject is willing and able to comply with the protocol requirements.
• \. Willing to record requested information in the daily diary. 12. Lives within the study site catchment area or within a reasonable distance from the site.
• \. Understands and signs an Institutional Review Board (IRB) approved informed consent form prior to undergoing any screening assessments (including fasting blood draw).
• \. Agrees not to participate in any other clinical trials during the course of this study.

You may not qualify if:

• Known hypersensitivity or contraindication to progestins.
• Abnormal Transvaginal Ultrasound (TVUS) or safety labs done during the screening period recognized as clinically significant by the investigator (or medically qualified designee).
• Greater than 10% body weight change over previous year or planned significant weight loss during the study related to bariatric surgery, dieting or other causes.
• Known or suspected current alcohol dependence syndrome, chronic marijuana use or any illicit drug use that may affect metabolism of the study product or study compliance.
• Undiagnosed abnormal genital bleeding.
• Undiagnosed vaginal discharge, lesions or abnormalities. Subjects diagnosed at screening with Chlamydia, or gonococcus infection may be included in the trial following treatment completion. In accordance with PI/medical designee assessment and local standards of practice, women with a history of genital herpes can be included if outbreaks are infrequent. Antiviral prophylactic therapy is permitted.
• Uncontrolled thyroid disorder.
• Current use of hormonal contraception including hormonal intrauterine device.
• Use of a long-acting injectable hormonal contraceptive (e.g., cyclofem or depomedroxyprogesterone acetate) within the past 9 months prior to enrollment unless the subject has had at least one spontaneous menstrual cycle (at least two menses) since the last injection.
• Recent use of hormonal oral, patch, intravaginal or intrauterine contraception unless that subject has had at least one complete menstrual cycle (at least two menses) since discontinuation before the treatment injection.
• Women who are breastfeeding or are within 30 days of discontinuing breastfeeding unless the subject has already had a menses following discontinuation of breastfeeding.
• Women planning to undergo major surgery during study participation.
• Women planning pregnancy during their anticipated months of study participation.
• Current or past deep vein thrombophlebitis or thromboembolic disorders.
• Known history of thrombophilia.

Sponsors & Collaborators

• Premier Research: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (7)

University of California, Davis

Davis, California, 95817, United States

Location

Comprehensive Women's Health Center

Denver, Colorado, 80230, United States

Location

Boston Medical Center Corporation

Boston, Massachusetts, 02118, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

MeSH Terms

Interventions

levonorgestrel butanoate

Study Officials

• Diana Blithe

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Program Director, NICHD

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 29, 2019
• Study Start: March 3, 2020
• Primary Completion: March 26, 2026
• Study Completion: March 26, 2026
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)