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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04143659
Recruitment Status : Not yet recruiting
First Posted : October 29, 2019
Last Update Posted : October 29, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Health Decisions

Brief Summary:
This is a Phase I multicenter, open-label, dose-ranging, two-dose PK and PD study of injectable LB at administered as a SQ or IM injection at 40 mg and subsequently at 80 mg SQ or IM depending on the pharmacokinetic and pharmacodynamic results obtained at 40 mg.

Condition or disease Intervention/treatment Phase
Healthy Women Female Contraception Biological: levonorgestrel butanoate (LB) injection Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase I Study to Evaluate the Pharmacokinetic and Pharmacodynamic Profile of Intramuscular or Subcutaneous Injections of Levonorgestrel Butanoate (LB) for Female Contraception
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Control

Arm Intervention/treatment
Experimental: LB injection 40mg intramuscular (IM)
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 40mg intramuscular (IM)
Biological: levonorgestrel butanoate (LB) injection
The study medication is LB Injectable Suspension, 40 mg/2mL (20 mg/mL). The formulation consists of a suspension of spray dried LB powder, with an approximate mean particle size of 13 micron, in an aqueous vehicle containing: super refined polysorbate 80 (Tween® 80), spray dried sorbitan monopalmitate (Span® 40), sodium carboxymethylcellulose, sodium phosphate dibasic anhydrous, sodium phosphate monobasic dihydrate, benzyl alcohol and water for injection, USP. Each vial contains 2 mL at 20mg/mL for a total of 40 mg.

Experimental: LB injection 40 mg subcutaneous (SC)
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 40mg subcutaneous (SC)
Biological: levonorgestrel butanoate (LB) injection
The study medication is LB Injectable Suspension, 40 mg/2mL (20 mg/mL). The formulation consists of a suspension of spray dried LB powder, with an approximate mean particle size of 13 micron, in an aqueous vehicle containing: super refined polysorbate 80 (Tween® 80), spray dried sorbitan monopalmitate (Span® 40), sodium carboxymethylcellulose, sodium phosphate dibasic anhydrous, sodium phosphate monobasic dihydrate, benzyl alcohol and water for injection, USP. Each vial contains 2 mL at 20mg/mL for a total of 40 mg.

Experimental: LB injection 80mg intramuscular (IM)
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 80mg intramuscular (IM)
Biological: levonorgestrel butanoate (LB) injection
The study medication is LB Injectable Suspension, 40 mg/2mL (20 mg/mL). The formulation consists of a suspension of spray dried LB powder, with an approximate mean particle size of 13 micron, in an aqueous vehicle containing: super refined polysorbate 80 (Tween® 80), spray dried sorbitan monopalmitate (Span® 40), sodium carboxymethylcellulose, sodium phosphate dibasic anhydrous, sodium phosphate monobasic dihydrate, benzyl alcohol and water for injection, USP. Each vial contains 2 mL at 20mg/mL for a total of 40 mg.

Experimental: LB injection 80mg Subcutaneous (SC)
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 80mg subcutaneous (SC)
Biological: levonorgestrel butanoate (LB) injection
The study medication is LB Injectable Suspension, 40 mg/2mL (20 mg/mL). The formulation consists of a suspension of spray dried LB powder, with an approximate mean particle size of 13 micron, in an aqueous vehicle containing: super refined polysorbate 80 (Tween® 80), spray dried sorbitan monopalmitate (Span® 40), sodium carboxymethylcellulose, sodium phosphate dibasic anhydrous, sodium phosphate monobasic dihydrate, benzyl alcohol and water for injection, USP. Each vial contains 2 mL at 20mg/mL for a total of 40 mg.




Primary Outcome Measures :
  1. Measurement of levonorgestrel serum concentrations [ Time Frame: 0, 2, 4, 6, 8, 24, 48, 120, 168, and 264 hours. Then weekly for up to 26 weeks. ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: Weekly up to 26 weeks ]
  2. Measurement of Endometrial thickness [ Time Frame: Weekly up to 26 weeks ]
  3. Steroid hormone (Estradiol) concentration [ Time Frame: Weekly up to 26 weeks ]
  4. Gonadotropin (Follicle Stimulating Hormone and Luteinizing Hormone) concentrations [ Time Frame: Weekly up to 26 weeks ]
  5. Sex Hormone Binding Globulin (SHGB) concentration [ Time Frame: Weekly up to 26 weeks ]
  6. Bleeding patterns (spotting and light, moderate or heavy bleeding) reported through weekly subject diaries [ Time Frame: Weekly up to 26 weeks ]
  7. Side effects of LB as measured by adverse events reported [ Time Frame: Weekly up to 26 weeks ]


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Good general health with no chronic medical conditions that result in periodic exacerbations that require significant medical care.
  2. Age between 18 and 40 years inclusive at the injection visit.
  3. BMI < 40 kg/m2.
  4. Intact uterus with at least one ovary.
  5. 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.
  6. Regular menstrual cycles that occur every 21-35 days:

6a. If subject is postpartum or post-second trimester abortion, she must have 3 menses (2 cycles) prior to enrollment.

6b. If subject had a first trimester abortion or pregnancy loss, she must have one spontaneous menses prior to enrollment.

7. Have a negative urine pregnancy test at the injection visit and no unprotected heterosexual intercourse for the previous 10 days.

8. 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).

8e. use copper IUD 9. In the opinion of the investigator, subject is willing and able to comply with the protocol requirements.

10. Subject is willing to record requested information in the daily diary. 11. Lives within the study site catchment area or within a reasonable distance from the site.

12. Understand and sign an IRB approved informed consent form prior to undergoing any screening assessments (including fasting blood draw).

13. Agree not to participate in any other clinical trials during the course of this study.

Exclusion Criteria:

  1. Known hypersensitivity or contraindication to progestins.
  2. Abnormal Transvaginal Ultrasound (TVUS) or safety labs done during the screening period recognized as clinically significant by the investigator (or medically qualified designee).
  3. 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.
  4. 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.
  5. Undiagnosed abnormal genital bleeding.
  6. Undiagnosed vaginal discharge, lesions or abnormalities. Subjects diagnosed at screening with BV, trichomonas, candida, 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.
  7. Uncontrolled thyroid disorder.
  8. Current use of hormonal contraception including hormonal intrauterine device.
  9. 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.
  10. 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.
  11. Women who are breastfeeding or are within 30 days of discontinuing breast feeding unless the subject has already had a menses following discontinuation of breastfeeding.
  12. Women planning to undergo major surgery during study participation.
  13. Women planning pregnancy during their anticipated months of study participation.
  14. Women who smoke > 15 cigarettes per day or who use >1 ml/day of nicotine-containing liquid for electronic cigarette must be evaluated by the PI for inclusion based on risk factors that would increase their risk for cardiovascular disease (CVD) and thromboembolism.
  15. Current or past deep vein thrombophlebitis or thromboembolic disorders.
  16. Known history of thrombophilia.
  17. Cerebrovascular or cardiovascular disease or increased risk for arterial thrombosis.
  18. Known or suspected carcinoma of the breast, endometrium, or any other known or suspected progestin-dependent neoplasia.
  19. Current or past medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive, unless she is stable on antidepressant medication.
  20. Have a current need for exogenous hormones or therapeutic anticoagulants.
  21. History of any other carcinoma (excluding basal cell carcinomas) unless in remission for more than 5 years.
  22. Active liver disease or screening LFTs greater than twice the upper limit or normal.
  23. Diastolic blood pressure (DBP) > 95 and Systolic blood pressure (SBP) > 145 mm Hg; (BP will be taken three times at approximately 5-minute intervals and the mean of the last two of the three measurements will be used to determine eligibility).
  24. Clinically significant abnormal serum chemistry or hematology values according to the Principal Investigator's judgment.
  25. Participation in another clinical trial involving an investigational drug or device within last the three months before treatment injection or planning to participate in another clinical trial during this study.
  26. Use of liver enzyme inducers within the last 90 days prior to screening or intention to use liver enzyme inducers during the study.
  27. Known HIV infection.
  28. Women who use any medications on the Exclusionary Medication List OR have used any within the past three months prior to the Injection visit.
  29. Have issues or concerns (in the judgement of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.
  30. Have known hypersensitivity to the active substance LB or any of the excipients of the study treatment.
  31. Use any medications that can interfere with the metabolism of hormonal contraceptives, antibiotics that can interfere with metabolism of hormonal contraceptives, or any drugs designated by the FDA as falling in the Pregnancy and Lactation narrative subsections (formerly Category D or X medications).
  32. Have previously participated in the study.
  33. Be a site staff member with delegated study responsibilities or a family member of, or have a close relationship with, a site staff member with delegated study responsibilities.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04143659


Locations
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United States, California
University of California, Davis
Davis, California, United States, 95817
Principal Investigator: Mitchell Creinin, MD         
United States, Colorado
Comprehensive Women's Health Center
Denver, Colorado, United States, 80230
Principal Investigator: Stephanie Teal, MD, MPH         
United States, Massachusetts
Boston Medical Center Corporation
Boston, Massachusetts, United States, 02118
Principal Investigator: Katharine White, MD, MPH         
United States, New York
Columbia University
New York, New York, United States, 10032
Principal Investigator: Carolyn Westhoff, MD, MSc         
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
Principal Investigator: Jeffrey Jensen, MMD, MPH         
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Principal Investigator: David Turok, MD         
United States, Virginia
Eastern Virginia Medical School
Norfolk, Virginia, United States, 23507
Principal Investigator: David F. Archer, MD         
Sponsors and Collaborators
Health Decisions
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Responsible Party: Health Decisions
ClinicalTrials.gov Identifier: NCT04143659    
Other Study ID Numbers: CCN021
First Posted: October 29, 2019    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Levonorgestrel
Norgestrel
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral