Healthy Participants
Conditions
Keywords
Obesity, Overweight, Oral contraceptives, Pharmacokinetics, Drug Interaction
Brief 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 3 cohorts, and each cohort will consist of 5 periods which include, Screening, Start, Up-titration, Maintenance, and Follow-up periods.
Interventions
DRUGAZD6234
AZD6234 will be administered as a subcutaneous injection in the abdomen.
DRUGEthinyl estradiol/Levonorgestrel (EE/LEVO)
EE/LEVO will be administered as combined oral tablets.
DRUGAcetaminophen (APAP)
APAP will be administered orally as a solution.
DRUGAZD9550
AZD9550 will be administered as a subcutaneous injection in the abdomen.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 75 Years
Healthy volunteers
Yes
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.
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 and cohort 2), 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 and cohort 3), history of acute or chronic pancreatitis or pancreatic amylase or lipase \>2×ULN at screening (cohort 2 and cohort 3), 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 and cohort 3). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve from time 0 to infinity (AUCinf) of EE and LEVO | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | To assess the safety and tolerability of AZD6234, co-administered AZD9550 and AZD6234, and AZD9550 with CoC EE/LEVO. |
| 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 | To assess the safety and tolerability of AZD6234, co-administered AZD9550 and AZD6234, and AZD9550 with CoC EE/LEVO. |
| 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 | To characterize the PK of single and multiple doses of AZD6234. |
| AUClast of AZD6234 | Cohort 1: At predefined intervals from Day 1 to Day 120 | To characterize the PK of single and multiple doses of AZD6234. |
| Cmax of AZD6234 | Cohort 1: At predefined intervals from Day 1 to Day 120 | To characterize the PK of single and multiple doses of AZD6234. |
| AUC0-168h of co-administered AZD6234 and AZD9550 | Cohort 2: At predefined intervals from Day 8 to Day 216 | To characterize the PK of single and multiple doses of co-administered AZD6234 and AZD9550. |
| AUClast of co-administered AZD6234 and AZD9550 | Cohort 2: At predefined intervals from Day 8 to Day 216 | To characterize the PK of single and multiple doses of co-administered AZD6234 and AZD9550. |
| Cmax of co-administered AZD6234 and AZD9550 | Cohort 2: At predefined intervals from Day 8 to Day 216 | To characterize the PK of single and multiple doses of co-administered AZD6234 and AZD9550. |
| AUC0-168h of AZD9550 | Cohort 3: At predefined intervals from Day 8 up to Day 272 | To characterize the PK of single and multiple doses of AZD9550. |
| AUClast of AZD9550 | Cohort 3: At predefined intervals from Day 8 up to Day 272 | To characterize the PK of single and multiple doses of AZD9550. |
| Cmax of AZD9550 | Cohort 3: At predefined intervals from Day 8 up to Day 272 | To characterize the PK of single and multiple doses of AZD9550. |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed