A Randomised, Open-Label Study to Evaluate the Relative and Absolute Bioavailability of Cotadutide in Healthy Subjects

NCT05294458 | Completed Phase 1

• 2 other identifiers: D5671C000092021-005442-15
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing the test medicine, cotadutide, for the potential treatment of non-alcoholic steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM) with chronic kidney disease. This healthy volunteer study will try to identify how two different concentrations of cotadutide are taken up by the body when dosed under the skin (subcutaneous injection). The study will also try to identify the absolute bioavailability of cotadutide (amount taken up by the body when dosed under the skin compared to an injection directly into the vein (intravenous)). This is a single-part, three-period study taking place at one non-NHS site in the UK and will involve 12 male and female (non-pregnant/non-lactating) volunteers aged 18-55. For each study period, on Day 1 volunteers will receive cotadutide as either a subcutaneous injection (into the stomach) or an intravenous injection following an overnight fast of at least 10 hours. The subcutaneous injections will be given as either a 1 mg/ml or 5 mg/ml concentration. The intravenous injection will be given as a 0.1 mg/ml concentration. Volunteers will be discharged on Day 4 and there will be a washout period of 7 days between dosing. Blood samples will be taken at regular intervals for pharmacokinetics and safety assessments from Day -1 to discharge. Volunteers will need to return for a follow up visit 28 (±2) days post-first dose for provisional of an anti-drug antibody sample and to ensure wellbeing

Conditions

Non-alcoholic Steatohepatitis; Type 2 Diabetes Mellitus (T2DM); Chronic Kidney Disease

Keywords

Steatohepatitis; Diabetes; Kidney disease

Outcome Measures

Primary Outcomes (4)

• Absolute bioavailability of the high and the low concentration cotadutide SC formulations

  Evaluation of the absolute bioavailability (F) of the SC formulations by comparison of AUCsubcut/AUCIV

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Maximum observed concentration (cmax)

  Assessment of pharmacokinetics and relative bioavailability of cotadutide solution for injection by measuring maximum observed concentration (cmax)

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Relative bioavailability of a high concentration cotadutide SC formulation in comparison to low concentration formulation, in the fasted state

  Pharmacokinetic parameters AUC0-t for cotadutide in the high concentration and low concentration regimens

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Relative bioavailability of a high concentration cotadutide SC formulation in comparison to low concentration formulation, in the fasted state

  Pharmacokinetic parameters AUC0-inf for cotadutide in the high concentration and low concentration regimens

  Collection of plasma samples from pre-dose to 72 hours post-dose.

Secondary Outcomes (13)

• Provide additional details on the single dose PK of cotadutide

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Provide additional details on the single dose PK of cotadutide

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Provide additional details on the single dose PK of cotadutide

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Provide additional details on the single dose PK of cotadutide

  Collection of plasma samples from pre-dose to 72 hours post-dose.

• Provide additional details on the single dose PK of cotadutide

  Collection of plasma samples from pre-dose to 72 hours post-dose.

Other Outcomes (2)

• To collect data on the size and shape of SC injection

  before and immediately after injection and up to 72 hours post-injection

• Temperature needed at the injection site to homogenize at the point of injection

  Before and immediately after injection and up to 72 hours post-injection

Study Arms (1)

Cotadutide solution for injection

EXPERIMENTAL

Period 1, subcutaneous injection of cotadutide solution Period 2, subcutaneous injection of cotadutide solution Period 3, subcutaneous injection of cotadutide solution

Drug: cotadutide solution for injection

Interventions

cotadutide solution for injection DRUG

cotadutide solution for injection

Cotadutide solution for injection

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 males or non-pregnant, non-lactating healthy females aged 18 to 55 years at the time of signing informed consent.
• Females must have a negative serum pregnancy test at screening and a negative urine pregnancy test on admission to the unit, must not be lactating, confirmed at screening and fulfil the criteria detailed in Section 9.4.
• Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Must be willing and able to communicate and participate in the whole study.
• Subjects must have been received both doses of the SARS-CoV-2 vaccine.
• Must agree to adhere to the contraception requirements defined in Section 9.4

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of any disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Evidence of renal impairment at screening, as indicated by an estimated eGFR of \<60 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• A personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2.
• Thyroid C-cell hyperplasia (calcitonin level \> 50 ng/L) or medullary thyroid carcinoma at screening.
• History of clinically significant cardiovascular, renal, hepatic, dermatological, respirator, neurological, psychiatric or gastrointestinal disease disorder including a history of pancreatitis.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at screening as judged by the investigator.
• Amylase and/or lipase \>1.5 × upper limit of normal (ULN) at screening
• Any clinically significant abnormal findings in vital signs, at screening and/or first admission to the study unit, as judged by the investigator.
• Any clinically significant abnormalities on 12-lead ECG, including but not limited to QTcF \>450 msec, at screening, as judged by the investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and human immunodeficiency virus (HIV) antibody.
• Evidence of current infection with SARS-Cov-2.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer. Note: subjects consented and screened, but not randomised in this study or a previous phase I study, are not excluded.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

Related Links

• The redacted CSR D5671C00009

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Fatty Liver; Diabetes Mellitus; Kidney Diseases

Interventions

Injections

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Somasekhara Menakuru, MBBS, MS, MRCS, DPM, MFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 24, 2022
• Study Start: March 28, 2022
• Primary Completion: September 12, 2022
• Study Completion: September 12, 2022
• Last Updated: July 20, 2025

Record last verified: 2025-07

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 rerefer 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

GB (1)