Study of the Effect of ITCA 650 on the PK/PD of Oral Contraceptive in Healthy Female Subjects

A Phase 1, Randomized, Double-blind, Placebo-Controlled, Crossover Study to Assess the Effect of ITCA 650 on the Pharmacokinetics and Pharmacodynamics of a Combination Oral Contraceptive in Healthy Premenopausal Female Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Premenopausal Female Volunteers
• Intervention / Treatment: Drug: ITCA 650 20/60 mcg/day, ITCA placebo; Drug: ITCA placebo, ITCA 650 20/60 mcg/day

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • QPS/Miami Research Associates
    • Orlando, Florida, United States, 32806
      • Compass Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; ITCA 650 20/60 mcg/day, ITCA placebo	Drug: ITCA 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
Experimental: Group 2; ITCA placebo, ITCA 650 20/60 mcg/day	Drug: ITCA 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum steady state plasma concentration (tmax,ss) for ethinyl estradiol and levonorgestrel	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.	baseline to 13 weeks
Apparent plasma clearance at steady-state (CL/Fss) for ethinyl estradiol and levonorgestrel		baseline to 13 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional Outcome Measure 1	Pharmacodynamics - FSH	13 weeks
Additional Outcome Measure 2	Pharmacodynamics - LH	13 weeks
Additional Outcome Measure 3	Pharmacodynamics - progesterone	13 weeks

Collaborators and Investigators

• Sponsor: Intarcia Therapeutics

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 18, 2015
• First Submitted That Met QC Criteria: December 23, 2015
• First Posted (Estimate): December 30, 2015

Study Record Updates

• Last Update Posted (Estimate): March 22, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: ITCA 650-CLP-116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO