A Study to Investigate the Effect of AZD6234 and a Combination of AZD9550 and AZD6234 on Pharmacokinetics of Combined Oral Contraceptive Ethinyl Estradiol/Levonorgestrel in Healthy Female Participants Living With Overweight or Obesity

AstraZeneca

Status and phase: Enrolling; Phase 1

Conditions: Healthy Participants

Treatments: Drug: AZD6234; Drug: Acetaminophen (APAP); Drug: Ethinyl estradiol/Levonorgestrel (EE/LEVO); Drug: AZD9550

Study type: Interventional

Funder types: Industry

Identifiers

NCT07013643

D8750C00006

Details and patient eligibility

About

This study will measure the effects of multiple doses of AZD6234 and a combination of AZD6234 and AZD9550 given as injection(s) on pharmacokinetics (PK) of combined oral contraceptive ethinyl estradiol (EE)/levonorgestrel (LEVO) in healthy female participants with obesity.

Full 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 and a combination of AZD6234 and AZD9550 on the PK, safety and tolerability of a combined oral contraceptive, ethinyl estradiol/levonorgestrel (EE/LEVO).

The study will have 2 cohorts, and each cohort will consist of 5 periods which include, Screening, Start, Up-titration, Maintenance, and Follow-up periods.

Enrollment: 50 estimated patients

Sex: Female

Ages: 35 to 75 years old

Volunteers: Accepts Healthy Volunteers

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 combined oral contraceptive assessment.

• Females of non-childbearing potential must be confirmed at the Screening Visit.

• Have a Body Mass Index (BMI) ≥ 25 kg/m2 inclusive and weigh at least 60 kg.

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, type I or type II diabetes mellitus, glycated hemoglobin (HbA1c) ≥ 6.5% at screening, history of neoplastic disease, basal calcitonin level >50 ng/L (50 pg/L) at screening (Cohort 2), history of acute or chronic pancreatitis or pancreatic amylase or lipase >2×ULN at screening (cohort 2), 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)).
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Cohort-1 AZD6234 + EE/LEVO + Acetaminophen (APAP)

Experimental group

Description:

Participants will receive combined oral contraceptive (EE/LEVO) and, separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 administration.

Treatment:

Drug: Ethinyl estradiol/Levonorgestrel (EE/LEVO)

Drug: Acetaminophen (APAP)

Drug: AZD6234

Cohort-2: AZD6234+AZD9550+EE/LEVO+APAP

Experimental group

Description:

All participants will receive combined oral contraceptive EE/LEVO and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous administered AZD6234 and AZD9550.

Treatment:

Drug: AZD9550

Drug: Ethinyl estradiol/Levonorgestrel (EE/LEVO)

Drug: Acetaminophen (APAP)

Drug: AZD6234