Healthy Adult Premenopausal Female Volunteers
Conditions
Brief summary
A Phase 1, randomized, double-blind, placebo-controlled, crossover study to assess the effect of ITCA 650 on the pharmacokinetics (PK) of once daily administration of Levora® (ethinyl estradiol 0.3 mg (EE) and levonorgestrel 0.15 mg (LNG) in healthy premenopausal female subjects.
Interventions
DRUGITCA 650 20/60 mcg/day, ITCA placebo
ITCA 650 osmotic mini pump delivering exenatide 20/60 mcg/day and Levora® for 28 days, followed by ITCA osmotic mini pump delivering placebo and Levora® for 28 days
DRUGITCA placebo, ITCA 650 20/60 mcg/day
ITCA osmotic mini pump delivering placebo and Levora® for 28 days, followed by Levora® and ITCA 650 osmotic mini pump delivering exenatide 20/60 mcg/day and Levora® for 28 days
Sponsors
Intarcia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Women of childbearing potential. * Use of a combination oral contraceptive ≥3 months immediately prior to screening. * Willing to use an additional adequate method of contraception during the study and until 1 additional menstrual cycle following the end-of-study (EOS) visit. Adequate methods of contraception for women of child bearing potential (WOCBP) include: mechanical products (ie, intrauterine device \[IUD\]-copper IUD); or barrier methods (eg, diaphragm, condoms, cervical cap) with spermicide. * Body mass index (BMI) ≥19 and ≤32 kg per meter squared. * Weight ≥50 and ≤100 kg. * Non-smoker or ex-smoker for \>6 months prior to screening (and has stopped using other nicotine products ≥2 weeks prior to screening).
Exclusion criteria
* History of type 1 or type 2 diabetes. * Received implanted contraceptives within 6 months prior to screening or injected contraceptives within 12 months prior to screening. * History or evidence, within the last 6 months prior to the Screening Visit, of myocardial infarction, coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention), unstable angina, or cerebrovascular accident or stroke. * History of uncontrolled hypertension. * History or evidence of acute or chronic pancreatitis. * History of liver disease. * History of medullary thyroid cancer or a personal or family history of multiple endocrine neoplasia type 2. * Poor thyroid, liver, or renal function. * Weight loss surgery or requires weight loss medications. * History of malignancy (not including basal or squamous cell carcinoma of the skin with past 5 years). (Subjects who have been disease free for 5 years may be included.) * Estrogen-dependent growths; undiagnosed vaginal bleeding. * History of active alcohol or substance abuse. * Regular daily consumption of more than 12 g of alcohol in any form. * Excessive in xanthine consumption (more than 5 cups of coffee or equivalent per day). * Treatment with medications that affect GI motility. * Any condition that would affect drug transit time or absorption (eg, gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, chronic diarrhea, vagotomy, chronic gastroesophageal reflux disease, malabsorption, colostomy, Crohn's disease, ulcerative colitis, or celiac sprue). * History of hypersensitivity to exenatide. * Contraindications or warnings according to the specific label(s) for EE and/or LNG therapy. * Women that are pregnant, lactating, or planning to become pregnant. * Any use of anticoagulants with the exception of those given in prophylaxis prior to surgical intervention. * History of or positive results on screening tests for hepatitis B and/or hepatitis C and/or human immunodeficiency virus (HIV). * Recent surgery or planned in-patient surgery, dental procedure, or hospitalization during the study. * History of migraine if aged \>35 years or has focal symptoms associated with migraine. * History of thrombophlebitis, thromboembolic disorders, or deep vein thrombophlebitis. * Fasting triglycerides above upper limit of normal at Screening. * Any gastrointestinal complaints within 7 days prior to first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve at steady state (AUCss) for ethinyl estradiol and levonorgestrel | from baseline to 13 weeks |
| Maximum steady state plasma concentration (Cmax,ss) for ethinyl estradiol and levonorgestrel | from baseline to 13 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to maximum steady state plasma concentration (tmax,ss) for ethinyl estradiol and levonorgestrel | baseline to 13 weeks | Immunogenicity parameters: \- ADA (anti-exenatide antibodies) Safety parameters: \- Treatment-emergent AEs (TEAEs) including any events local to the placement site, clinical laboratory measurements, ECGs, vital signs and physical examinations. |
| Apparent plasma clearance at steady-state (CL/Fss) for ethinyl estradiol and levonorgestrel | baseline to 13 weeks | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Additional Outcome Measure 2 | 13 weeks | Pharmacodynamics - LH |
| Additional Outcome Measure 3 | 13 weeks | Pharmacodynamics - progesterone |
| Additional Outcome Measure 1 | 13 weeks | Pharmacodynamics - FSH |
Countries
United States
Outcome results
None listed