Clinical trial NCT06132841: A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese
Official title: A Phase I Randomized, Single-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 Following Repeat Dose Administration in Participants With Overweight or Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Overweight
Obesity
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-11-15
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 142
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A study in healthy male and female participants of non-childbearing and childbearing potential who have overweight or obesity

Detailed description: The study will comprise of:

* A Screening Period of maximum 32 days (from Day -35 to Day -3).
* A Treatment Period of 6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3) and 26 weeks (Cohort 4) during which the participants will receive the study drug during residency at clinical unit.
* A Follow-up Visit after the last dose of study drug.

This study with repeated dosing of AZD6234 consists of 4 cohorts. For cohorts 1,2 and 3, eligible participants will be randomized to AZD6234 and placebo in a 3:1 ratio. For Cohort 4, eligible participants will be randomized in a 4:1:4:1 ratio.

Eligibility criteria: Inclusion Criteria:

* Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
* All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
* Have a BMI between 25 and 40 kg/m2 inclusive (at the time of screening) and weigh at least 60 kg.
* Participant must have an evaluable, pre-randomization MRI, as confirmed by the core laboratory review (Cohort 4 only).
* Cohort 4 only: Females of childbearing potential who use adequate protection (oral contraceptives are not permitted).

Exclusion Criteria:

* History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
* 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 within 4 weeks of the first administration of IMP.
* Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal STT wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
* Known or suspected history of drug abuse, smoking, alcohol abuse or cotinine at screening.
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD6234.
* Has received prescription or non-prescription medication for weight loss within the last 3 months.
* Self-reported weight change of \> 5 kg in the last 3 months prior to screening.
* Previous or planned (within study period) bariatric surgery or fitting of a weight loss device (eg, gastric balloon or duodenal barrier).
* Participants who follow vegan diet or have medical dietary restrictions.
* Participants who cannot communicate reliably with the Investigator.
* Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
* Contra-indication to MRI: such as participants with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field; participants with history of extreme claustrophobia or participant cannot fit inside the MRI scanner cavity (Cohort 4 only).

Primary outcomes:
measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events(SAE)
timeFrame: From Screening (Day -35 to Day -3) to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
Secondary outcomes:
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
measure: Area under the plasma concentration-time (AUClast)
timeFrame: From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
measure: Area under plasma concentration-time curve from zero to infinity (AUCinf)
timeFrame: From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or Day 225 (Cohort 4)
measure: Area under concentration time curve in the dosing interval (AUCtau)
timeFrame: From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
measure: Change from baseline in body weight of participants
timeFrame: From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
measure: Change from baseline in Body Mass Index (BMI) of participants
timeFrame: From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
measure: Percentage change from baseline in fasting insulin
timeFrame: From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
measure: Change from baseline in absolute level of fasting insulin of participants
timeFrame: From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
measure: Prevalence of anti-drug antibodies (ADAs) to AZD6234
timeFrame: Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4)
measure: Incidence of ADAs to AZD6234
timeFrame: Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) to Day 183 (Cohort 4)
measure: ADA titer
timeFrame: Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
city: Berlin
country: Germany
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: