A Study to Investigate the Effect of AZD6234, AZD9550, 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

Official title

An Open-label, Single-sequence Multiple Cohort Study to Assess the Effect of Multiple Doses of AZD6234, AZD9550, and a Combination of AZD9550 and AZD6234 on the Pharmacokinetics of Single Doses of Combined Oral Contraceptive Ethinyl Estradiol/Levonorgestrel in Healthy Female Participants Living With Overweight or Obesity

Overview

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.

Interventions

• Drug AZD6234
  AZD6234 will be administered as a subcutaneous injection in the abdomen.
• Drug Ethinyl estradiol/Levonorgestrel (EE/LEVO)
  EE/LEVO will be administered as combined oral tablets.
• Drug Acetaminophen (APAP)
  APAP will be administered orally as a solution.
• Drug AZD9550
  AZD9550 will be administered as a subcutaneous injection in the abdomen.

Primary outcome measures

• Area under the concentration-time curve from time 0 to infinity (AUCinf) of EE and LEVO [Time frame: Cohort 1: At predefined intervals from Day -5 up to Day 99; Cohort 2 : At pre-defined interval from Day -5 up to Day 169; Cohort 3: At predefined intervals from Day -5 up to Day 225; Cohort 4: At predefined intervals from Day -5 up to Day 253]
• Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of EE and LEVO [Time frame: Cohort 1: At predefined intervals from Day -5 up to Day 99; Cohort 2 : At pre-defined interval from Day -5 up to Day 169; Cohort 3: At predefined intervals from Day -5 up to Day 225; Cohort 4: At predefined intervals from Day -5 up to Day 253]
• Maximum plasma concentration (Cmax) of EE and LEVO [Time frame: Cohort 1: At predefined intervals from Day -5 up to Day 99; Cohort 2 : At pre-defined interval from Day -5 up to Day 169; Cohort 3: At predefined intervals from Day -5 up to Day 225; Cohort 4: At predefined intervals from Day -5 up to Day 253]
• Time to reach maximum drug concentration in plasma (tmax) of EE and LEVO [Time frame: Cohort 1: At predefined intervals from Day -5 up to Day 99; Cohort 2 : At pre-defined interval from Day -5 up to Day 169; Cohort 3: At predefined intervals from Day -5 up to Day 225; Cohort 4: At predefined intervals from Day -5 up to Day 253]
• Elimination half-life (t1/2λz) of EE and LEVO [Time frame: Cohort 1: At predefined intervals from Day -5 up to Day 99; Cohort 2 : At pre-defined interval from Day -5 up to Day 169; Cohort 3: At predefined intervals from Day -5 up to Day 225; Cohort 4: At predefined intervals from Day -5 up to Day 253]

Secondary outcome measures (11)

• Number of participants with adverse events (AEs) [Time frame: Cohort 1: Up to Day 120; Cohort 2: Up to Day 216; Cohort 3: Up to Day 272; Cohort 4: Up to Day 300]
• Number of participants developing detectable anti-drug antibodies (ADAs) against AZD6234 and AZD9550 [Time frame: Cohort 1: At predefined intervals from Day -2 up to Day 120; Cohort 2: At predefined intervals from Day -2 up to Day 216; Cohort 3: At predefined intervals from Day -2 up to Day 272; ; Cohort 4: At predefined intervals from Day -2 up to Day 300]
• Area under plasma concentration-time curve from time 0 to 168 hours postdose (AUC0-168h) of AZD6234 [Time frame: Cohort 1: At predefined intervals from Day 1 to Day 120]
• AUClast of AZD6234 [Time frame: Cohort 1: At predefined intervals from Day 1 to Day 120]
• Cmax of AZD6234 [Time frame: Cohort 1: At predefined intervals from Day 1 to Day 120]
• AUC0-168h of co-administered AZD6234 and AZD9550 [Time frame: Cohort 2: At predefined intervals from Day 8 to Day 216; Cohort 4: At predefined intervals from Day 78 to Day 300]
• AUClast of co-administered AZD6234 and AZD9550 [Time frame: Cohort 2: At predefined intervals from Day 8 to Day 216; Cohort 4: At predefined intervals from Day 78 to Day 300]
• Cmax of co-administered AZD6234 and AZD9550 [Time frame: Cohort 2: At predefined intervals from Day 8 to Day 216; Cohort 4: At predefined intervals from Day 78 to Day 300]
• AUC0-168h of AZD9550 [Time frame: Cohort 3: At predefined intervals from Day 8 up to Day 272]
• AUClast of AZD9550 [Time frame: Cohort 3: At predefined intervals from Day 8 up to Day 272]
• Cmax of AZD9550 [Time frame: Cohort 3: At predefined intervals from Day 8 up to Day 272]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Research Site — Glendale
• Research Site — Brooklyn

Identifiers

NCT: NCT07013643 · D8750C00006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗