Assess the Safety, Tolerability, and Pharmacokinetics of AZD6234 Following Single Ascending Dose Administration to Healthy Subjects Who Are Overweight or Obese

NCT05511025 | Completed Phase 1 FDA Drug

• 1 other identifier: D8750C00001
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

A study in healthy male and female participants of non-childbearing potential who are overweight or obese.

Conditions

Healthy Participants

Keywords

Overweight; Obese; Non-childbearing

Outcome Measures

Primary Outcomes (1)

• Number of participants with AEs and Serious Adverse Events(SAE)

  The safety and tolerability of AZD6234 following subcutaneous and/or intravenous administration of single ascending doses in healthy participants, including Japanese participants, who are overweight or obese will be assessed.

  From Screening until Follow up (Day 43)

Secondary Outcomes (16)

• Maximum observed plasma drug concentration (Cmax)

  From Day 1 until Follow up (Day 43)

• Area under the plasma concentration-time (AUClast)

  From Day 1 until Follow up (Day 43)

• Area under plasma concentration-time curve from zero to infinity (AUCinf)

  From Day 1 until Follow up (Day 43)

• Time to reach maximum observed concentration (tmax)

  From Day 1 until Follow up (Day 43)

• Terminal rate constant (λz)

  From Day 1 until Follow up (Day 43)

Study Arms (8)

Cohort 1

EXPERIMENTAL

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 2

EXPERIMENTAL

Participants will receive a single dose of AZD6234 via an SC injection and matching volume of the placebo as a solution via SC injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 3

EXPERIMENTAL

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 4

EXPERIMENTAL

Participants will receive single ascending doses of AZD6234 via IV injection and matching volumes of the placebo as a solution via IV injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 5

EXPERIMENTAL

One dose level for SC administration is planned to be investigated for Japanese participants only

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 6

EXPERIMENTAL

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 7

EXPERIMENTAL

Participants will receive single ascending doses of AZD6234 via SC injection and matching volumes of the placebo as a solution via SC injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Cohort 8

EXPERIMENTAL

Participants will receive AZD6234 via SC injection and matching volumes of placebo as a solution via SC injection

Drug: AZD6234; Drug: Placebo; Combination Product: Acetaminophen

Interventions

AZD6234 DRUG

Participants will receive a single dose of AZD6234 as a solution via SC or IV injection

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Cohort 8

Placebo DRUG

Participants will receive matching volumes of the placebo as a solution via SC or IV injection

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Cohort 8

Acetaminophen COMBINATION_PRODUCT

Participants will receive a single dose of acetaminophen as part of a meal

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Cohort 8

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• 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:
• (i) Post menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and Follicle stimulating hormone (FSH) levels in the post menopausal range.
• (ii) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Have a body mass index (BMI) of 25 to 35 kg/m2 inclusive (at the time of screening) and weigh at least 50 kg.
• For the Japanese cohort(s):
• Participant is a native of Japan; defined as having both parents and four grandparents who are Japanese. This includes second and third generation subjects of Japanese descent whose parents or grandparents are living in a country other than Japan.
• Have a BMI of 23 to 35 kg/m2 inclusive (at the time of screening) and weigh at least 50 kg.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, including:
• (i) Gastroparesis (or similar) requiring treatment, or (ii) Previous surgery of the upper gastrointestinal tract, or (iii) Cardiovascular disease, including but not limited to sick sinus syndrome, valvular disease, and cardiomyopathy, or (iv) Neuromuscular or neurogenic disease, or (v) Severe vitamin D deficiency \< 12 ng/dL (as assessed by screening laboratory results or history), or (vi) Type 1 or type 2 diabetes mellitus.
• 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 laboratory values with the following deviations:
• (i) Alanine aminotransferase \> Upper limit of normal (ULN) (ii) Aspartate aminotransferase \> ULN (iii) eGFR \< 60 ml/min/1.73 m2 (calculated using the CKD EPI formula) (iv) White blood cell count \< LLN (v) Hemoglobin \< LLN (vi) Total calcium or corrected calcium/ionized calcium \< LLN or \> ULN
• Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
• (i) Systolic Blood pressure (BP) \< 90 mmHg or \> 140 mmHg. (ii) Diastolic BP \< 50 mmHg or \> 90 mmHg. (iii) Heart rate \< 55 or \> 85 beats per minute (bpm)
• 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.
• Participants who are vegans or have medical dietary restrictions.
• Vulnerable participants, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Overweight; Obesity

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 22, 2022
• Study Start: September 20, 2022
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (2)