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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Area under the concentration-time curve from time 0 to infinity (AUCinf) of EE and LEVO
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort-2: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X1) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: Ethinyl estradiol/Levonorgestrel (EE/LEVO) (Drug)
Cohort-2: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X1) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: Acetaminophen (APAP) (Drug)
Cohort-2: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X1) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: AZD6234 (Drug)
Cohort-2: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X1) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: AZD9550 (Drug)
Cohort-3: AZD9550 + EE/LEVO + APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD9550 administration.
干预措施: Acetaminophen (APAP) (Drug)
Cohort-3: AZD9550 + EE/LEVO + APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD9550 administration.
干预措施: Ethinyl estradiol/Levonorgestrel (EE/LEVO) (Drug)
Cohort-1: AZD6234 + EE/LEVO + Acetaminophen (APAP)
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 administration.
干预措施: Acetaminophen (APAP) (Drug)
Cohort-1: AZD6234 + EE/LEVO + Acetaminophen (APAP)
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 administration.
干预措施: Ethinyl estradiol/Levonorgestrel (EE/LEVO) (Drug)
Cohort-3: AZD9550 + EE/LEVO + APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD9550 administration.
干预措施: AZD9550 (Drug)
Cohort-4: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X2) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: Ethinyl estradiol/Levonorgestrel (EE/LEVO) (Drug)
Cohort-4: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X2) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: Acetaminophen (APAP) (Drug)
Cohort-4: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X2) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: AZD6234 (Drug)
Cohort-1: AZD6234 + EE/LEVO + Acetaminophen (APAP)
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 administration.
干预措施: AZD6234 (Drug)
Cohort-4: AZD6234+AZD9550+EE/LEVO+APAP
All participants will receive CoC (EE/LEVO) and separately, APAP, treatments throughout the study during the up-titration and maintenance periods of subcutaneous AZD6234 (up to a maximum dose of Dose X2) and AZD9550 (up to a maximum dose of Dose Y1) administration.
干预措施: AZD9550 (Drug)
结局指标
主要结局
Area under the concentration-time curve from time 0 to infinity (AUCinf) of EE and LEVO
时间窗: 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
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of EE and LEVO
时间窗: 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
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Maximum plasma concentration (Cmax) of EE and LEVO
时间窗: 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
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Time to reach maximum drug concentration in plasma (tmax) of EE and LEVO
时间窗: 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
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Elimination half-life (t1/2λz) of EE and LEVO
时间窗: 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
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Area under the concentration-time curve from time 0 to infinity (AUCinf) of EE and LEVO
时间窗: 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 272
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of EE and LEVO
时间窗: 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 272
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Maximum plasma concentration (Cmax) of EE and LEVO
时间窗: 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 272
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Time to reach maximum drug concentration in plasma (tmax) of EE and LEVO
时间窗: 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 272
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
Elimination half-life (t1/2λz) of EE and LEVO
时间窗: 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 272
To assess the effect of multiple doses of AZD6234, multiple doses of co-administered AZD9550 and AZD6234, and multiple doses of AZD9550 on the PK of single doses of CoC EE/LEVO.
次要结局
- Number of participants with adverse events (AEs)(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(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)
- AUC0-168h of co-administered AZD6234 and AZD9550(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(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(Cohort 2: At predefined intervals from Day 8 to Day 216; Cohort 4: At predefined intervals from Day 78 to Day 300)
- Number of participants with adverse events (AEs)(Cohort 1: Up to Day 120; Cohort 2: Up to Day 216; Cohort 3: Up to Day 272)
- Number of participants developing detectable anti-drug antibodies (ADAs) against AZD6234 and AZD9550(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)
- Area under plasma concentration-time curve from time 0 to 168 hours postdose (AUC0-168h) of AZD6234(Cohort 1: At predefined intervals from Day 1 to Day 120)
- AUClast of AZD6234(Cohort 1: At predefined intervals from Day 1 to Day 120)
- Cmax of AZD6234(Cohort 1: At predefined intervals from Day 1 to Day 120)
- AUC0-168h of co-administered AZD6234 and AZD9550(Cohort 2: At predefined intervals from Day 8 to Day 216)
- AUClast of co-administered AZD6234 and AZD9550(Cohort 2: At predefined intervals from Day 8 to Day 216)
- Cmax of co-administered AZD6234 and AZD9550(Cohort 2: At predefined intervals from Day 8 to Day 216)
- AUC0-168h of AZD9550(Cohort 3: At predefined intervals from Day 8 up to Day 272)
- AUClast of AZD9550(Cohort 3: At predefined intervals from Day 8 up to Day 272)
- Cmax of AZD9550(Cohort 3: At predefined intervals from Day 8 up to Day 272)