Summary
This study will measure the effects of multiple doses of AZD6234, AZD9550 and a combination of AZD9550 and AZD6234 given as injection(s) on pharmacokinetics (PK) of combined oral contraceptive (CoC) ethinyl estradiol (EE)/levonorgestrel (LEVO) in healthy female participants with obesity.
Detailed Description
This is a Phase I, open-label, single-sequence, multiple-cohort study which will be performed at multiple study sites in healthy females of childbearing and non-childbearing potential.
The purpose of this study is to investigate the effect of AZD6234, AZD9550 and a combination of AZD9550 and AZD6234 on the PK, safety and tolerability of a CoC, ethinyl estradiol/levonorgestrel (EE/LEVO).
The study will have 4 cohorts, and each cohort will consist of 5 periods which include, Screening, Start, Up-titration, Maintenance, and Follow-up periods.
Eligibility Criteria
Age Range: 35 years to 75 years
Inclusion Criteria:
* All participants must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
* Females of childbearing potential must not be lactating and if heterosexually active, must agree to use an approved method of highly effective contraception.
o Hormonal contraceptives and estrogen-containing hormonal methods of birth control are not permitted due to potential effect and influence on the results using a CoC assessment.
* Females of non-childbearing potential must be confirmed at the Screening Visit.
* Have a Body Mass Index (BMI) between 25 and 40 kg/m2, both inclusive and weigh at least 60 kg for Cohorts 1, 2, and 3 and a BMI of \> 30 kg/m2 for Cohort 4.
Exclusion Criteria:
* History of any clinically important disease or disorder (gastroparesis, deep vein thrombosis, venous thromboembolism, previous surgery of the upper gastrointestinal tract, cardiovascular disease, neuromuscular or neurogenic disease, severe vitamin D deficiency (cohort 1, cohort 2 and cohort 4), type I or type II diabetes mellitus, glycated hemoglobin (HbA1c) ≥ 6.5% at screening, history of neoplastic disease (cohort 2, cohort 3 and cohort 4), basal calcitonin level \>50 ng/L (50 pg/L) at screening (cohort 2, cohort 3 and cohort 4), history of acute or chronic pancreatitis or pancreatic amylase or lipase \>2×ULN at screening (cohort 2, cohort 3 and cohort 4), prior history of cholecystectomy or untreated cholelithiasis and personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN2) (cohort 2, cohort 3 and cohort 4).
* History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Any clinically important illness, medical/surgical procedure, or trauma.
* Any laboratory values with deviations or clinically important abnormalities in clinical chemistry, hematology, or urinalysis.
* Any positive result on screening for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb) or Human immunodeficiency virus (HIV).
* Abnormal vital signs.
* Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12 lead electrocardiogram (ECG), at screening.
* Current smokers or those who have smoked or used nicotine products.
* Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
* Statin treatment within 4 weeks prior to the start of study treatment.
* Current use of estrogen-containing products.