Type 2 DiabetesPhase 1NCT05694741
A Study to Assess Safety, Tolerability, and Pharmacokinetics of AZD0186
A Phase 1 study testing AZD0186 in people with Type 2 Diabetes, run by AstraZeneca at 1 site in United States.
Trial summary
This study will assess the safety, tolerability, and pharmacokinetics of AZD0186 following single ascending doses (SAD) via oral administration in healthy adult participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- AZD0186
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Dec 2022to 10 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects 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.
- Have a BMI between:
- Part 1: 18 to 32 kg/m2 inclusive,
- Part 2 and Part 3: 18 to 32 kg/m2 inclusive,
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- and weigh at least 50 kg (males and females).
- Provision of signed, written, and dated informed consent for optional genetic/biomarker research.
- For the healthy Japanese cohort (Part 2): healthy subjects are to be Japanese (eg, natives of Japan or Japanese Americans), defined as having both parents and 4 grandparents who are Japanese.
- For the healthy Chinese cohort (Part 3): healthy male and female (of non-childbearing potential) healthy Chinese subjects for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years.
Who cannot join
- History of any clinically important disease or disorder which may either put the healthy subject at risk because of participation in the study,or influence the results or the healthy subject'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.
- Presence of any retinal (including intraretinal) abnormality detected by ophthalmological examination including indirect ophthalmoscopy, fundoscopy or OCT.
- Presence of any factors that predispose to retinal detachment including lattice degeneration, retinal hole, or high myopia (-10 diopters or higher) found on ophthalmological examination.
- History of retinal detachment in either eye.
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- History of treated or untreated retinal holes.
- Any clinically important abnormalities across the ophthalmological examinations.
- Any laboratory values with the following deviations:
- Alanine aminotransferase > ULN
- Aspartate aminotransferase > ULN
- eGFR < 90 mL/minute/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula)
- White blood cell count < LLN
- Hemoglobin < LLN
- Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV.
- Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
- Systolic BP < 90 mmHg or > 140 mmHg.
- Diastolic BP < 50 mmHg or > 90 mmHg.
- Heart rate < 45 or > 85 bpm.
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG that may interfere with the interpretation of QTc interval changes, including abnormal ST and T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
- Known or suspected history of drug abuse.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months.
- History of alcohol abuse or excessive intake of alcohol.
- Positive screen for drugs of abuse or cotinine at screening or admission to the Clinical Unit or positive screen for alcohol on admission to the Clinical Unit prior to the first administration of the IMP.
- 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 GLP-1 RA.
- Any condition that would have interfered with the evaluation of the IMP or interpretation of subject safety or study results.
- Lifetime history of schizophrenia or other psychosis or bipolar disorder or suicide attempts, major depressive disorder, or self-reported suicidal ideation.
- Healthy subjects with a history of MTC, multiple endocrine neoplasia syndrome type 2, or healthy subjects with a screening/baseline serum calcitonin ≥ 50 pg/mL.
- History of gastrointestinal abnormality that could affect gastrointestinal motility.
- Excessive intake of caffeine containing drinks or food.
- Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
- Has received another new chemical entity within 30 days or 5 half-lives of the first administration of IMP in this study.
- Previous bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Randomized, Single-blind, Placebo-controlled, First-in-Human and Sequential Group Study to Assess Safety, Tolerability, and Pharmacokinetics of AZD0186 Following Single Ascending Doses Via Oral Administration
This study will assess the safety, tolerability, and pharmacokinetics of AZD0186 following single ascending doses (SAD) via oral administration in healthy adult participants.
Read the detailed description
This is a Phase 1, First-in-Human (FIH), randomized, single-blind, sponsor-open, placebo-controlled, SAD sequential group design study.
This study consists of four parts: Part 1, Part 2, Part 3, and Part 4.
The study will comprise of the following:
Part 1, Part 2, Part 3, and Part 4:
- A Screening Period of maximum 28 days.
- A Treatment Period during which subjects will be resident at the Clinical Unit from 2 days before IMP (Investigational Medicinal Product) administration (Day -2) until at least 48 hours after IMP administration; discharged on Day 3.
Part 4:
- A second Treatment Period during which subjects will be resident at the Clinical Unit from the day of the Follow-up Visit (Day 7 ±1 days after the last IMP dose) until at least 48 hours after the second IMP administration; discharged on Day 10.
Part 1, Part 2, Part 3, and Part 4:
- A Follow-up Visit after 7 (Part 1, Part 2, and Part 3) or 14 (Part 4) ±1 day after the last IMP dose.
- Conditions
- Type 2 Diabetes
- Being tested
- AZD0186, Placebo
- Keywords
- Type 2 Diabetes, Hyperglycemia, Glucagon-like peptide-1 receptor agonists
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0186Drug
Subjects will receive AZD0186 orally.
PlaceboDrug
Subjects will receive placebo orally.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (healthy volunteers) | Experimental | The planned number of cohorts is up to 6 cohorts; additional cohorts may be included if it is considered necessary to repeat a dose level or if additional dose steps are required for safety purposes. Six subjects will receive AZD0186, and two subjects will receive placebo. Receives: Drug: AZD0186; Drug: Placebo |
| Cohort 2 (healthy Japanese volunteers) | Experimental | The planned number of Japanese cohorts is 1, but more than 1 cohort may be included if the SRC considers it necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Japanese cohort. Receives: Drug: AZD0186; Drug: Placebo |
| Cohort 3 (healthy Chinese volunteers) | Experimental | The planned number of Chinese cohorts is 1, but more than 1 cohort may be included if it is considered necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Chinese cohort. Receives: Drug: AZD0186; Drug: Placebo |
| Cohort 4 (healthy volunteers - food effect) | Experimental | One of the Part 1 cohorts (planned for Cohort 6, can be updated pending emerging data) will continue into the food-effect part after a washout period. This part will be initiated after SRC review of all available data from preceding cohorts in this study. Receives: Drug: AZD0186; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs), and Serious Adverse Events (SAEs)
The safety and tolerability of AZD0186 following oral single ascending doses in healthy subjects (Part 1 and Part 4), in healthy Japanese subjects (Part 2), and in healthy Chinese subjects (Part 3) will be assessed.
Measured: Up to the Follow-up Visit (approximately 6 weeks)
Secondary outcomes (3)
Area under plasma concentration-time curve from zero to infinity (AUCinf)
The AUCinf of AZD0186 following oral single ascending doses will be characterized.
Measured: Day 1 to Day 3
Area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUClast)
The AUClast of AZD0186 following oral single ascending doses will be characterized.
Measured: Day 1 to Day 3
Maximum observed concentration (Cmax)
The Cmax of AZD0186 following oral single ascending doses will be characterized.
Measured: Day 1 to Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2023
- Study start20 Dec 2022
- Primary completion10 May 2023
- Study completion10 May 2023
Why it stopped: The decision was based on the overall data profile obtained from this study which did not demonstrate sufficient differentiation to surpass the current standard of care.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Placebo-control
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Esther Yoon, MD, Principal investigator, PAREXEL Early Phase Clinical Unit-Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05694741
- Sponsor's protocol ID
- D8740C00001
- Status last verified
- Dec 2024
- First submitted
- 20 Dec 2022
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual participant-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Randomized, Single-blind, Placebo-controlled, First-in-Human and Sequential Group Study to Assess Safety, Tolerability, and Pharmacokinetics of AZD0186 Following Single Ascending Doses Via Oral Administration
- ClinicalTrials.gov ID
- NCT05694741
- Acronym / sponsor ID
- D8740C00001
- Conditions
- Type 2 Diabetes
- Keywords
- Type 2 Diabetes, Hyperglycemia, Glucagon-like peptide-1 receptor agonists
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision was based on the overall data profile obtained from this study which did not demonstrate sufficient differentiation to surpass the current standard of care.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 20 Dec 2022 (actual)
- Primary completion
- 10 May 2023 (actual)
- Study completion
- 10 May 2023 (actual)
- First posted
- 23 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, tolerability, and pharmacokinetics of AZD0186 following single ascending doses (SAD) via oral administration in healthy adult participants.
Detailed description
This is a Phase 1, First-in-Human (FIH), randomized, single-blind, sponsor-open, placebo-controlled, SAD sequential group design study.
This study consists of four parts: Part 1, Part 2, Part 3, and Part 4.
The study will comprise of the following:
Part 1, Part 2, Part 3, and Part 4:
- A Screening Period of maximum 28 days.
- A Treatment Period during which subjects will be resident at the Clinical Unit from 2 days before IMP (Investigational Medicinal Product) administration (Day -2) until at least 48 hours after IMP administration; discharged on Day 3.
Part 4:
- A second Treatment Period during which subjects will be resident at the Clinical Unit from the day of the Follow-up Visit (Day 7 ±1 days after the last IMP dose) until at least 48 hours after the second IMP administration; discharged on Day 10.
Part 1, Part 2, Part 3, and Part 4:
- A Follow-up Visit after 7 (Part 1, Part 2, and Part 3) or 14 (Part 4) ±1 day after the last IMP dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 4
- Model description
- Placebo-control
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (healthy volunteers) | Experimental | Drug: AZD0186, Drug: PlaceboThe planned number of cohorts is up to 6 cohorts; additional cohorts may be included if it is considered necessary to repeat a dose level or if additional dose steps are required for safety purposes. Six subjects will receive AZD0186, and two subjects will receive placebo. |
| Cohort 2 (healthy Japanese volunteers) | Experimental | Drug: AZD0186, Drug: PlaceboThe planned number of Japanese cohorts is 1, but more than 1 cohort may be included if the SRC considers it necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Japanese cohort. |
| Cohort 3 (healthy Chinese volunteers) | Experimental | Drug: AZD0186, Drug: PlaceboThe planned number of Chinese cohorts is 1, but more than 1 cohort may be included if it is considered necessary to repeat a dose level or if additional dose steps are required. No sentinel dosing will be performed for the Chinese cohort. |
| Cohort 4 (healthy volunteers - food effect) | Experimental | Drug: AZD0186, Drug: PlaceboOne of the Part 1 cohorts (planned for Cohort 6, can be updated pending emerging data) will continue into the food-effect part after a washout period. This part will be initiated after SRC review of all available data from preceding cohorts in this study. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects 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.
- Have a BMI between:
- Provision of signed, written, and dated informed consent for optional genetic/biomarker research.
Key exclusion criteria (35 listed)
- History of any clinically important disease or disorder which may either put the healthy subject at risk because of participation in the study,or influence the results or the healthy subject'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.
- Presence of any retinal (including intraretinal) abnormality detected by ophthalmological examination including indirect ophthalmoscopy, fundoscopy or OCT.
- Presence of any factors that predispose to retinal detachment including lattice degeneration, retinal hole, or high myopia (-10 diopters or higher) found on ophthalmological examination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD0186Subjects will receive AZD0186 orally. | Drug | Cohort 1 (healthy volunteers), Cohort 2 (healthy Japanese volunteers), Cohort 3 (healthy Chinese volunteers), Cohort 4 (healthy volunteers - food effect) |
| PlaceboSubjects will receive placebo orally. | Drug | Cohort 1 (healthy volunteers), Cohort 2 (healthy Japanese volunteers), Cohort 3 (healthy Chinese volunteers), Cohort 4 (healthy volunteers - food effect) |
Primary outcome
Adverse Events (AEs), and Serious Adverse Events (SAEs)
Time frame: Up to the Follow-up Visit (approximately 6 weeks)
The safety and tolerability of AZD0186 following oral single ascending doses in healthy subjects (Part 1 and Part 4), in healthy Japanese subjects (Part 2), and in healthy Chinese subjects (Part 3) will be assessed.
3 secondary outcomes
Area under plasma concentration-time curve from zero to infinity (AUCinf)
Time frame: Day 1 to Day 3
Area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUClast)
Time frame: Day 1 to Day 3
Maximum observed concentration (Cmax)
Time frame: Day 1 to Day 3
Results and safety
The study was stopped early (reason given: The decision was based on the overall data profile obtained from this study which did not demonstrate sufficient differentiation to surpass the current standard of care.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- D8740C00001\_Redacted\_CSR SynopsisLink provided by the sponsor.
- D8740C00001\_link to the results already presented on AZCTLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual participant-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Esther Yoon, MD principal investigator
PAREXEL Early Phase Clinical Unit-Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0186 in people with Type 2 Diabetes, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The decision was based on the overall data profile obtained from this study which did not demonstrate sufficient differentiation to surpass the current standard of care.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs), and Serious Adverse Events (SAEs) (time frame: Up to the Follow-up Visit (approximately 6 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.