T2DM With NAFLDPhase 1NCT02826525
AZD4076 in Type 2 Diabetic Subjects With Non-Alcoholic Fatty Liver Disease.
A Phase 1 study testing AZD4076 in people with T2DM With NAFLD, run by AstraZeneca.
Trial summary
This is a phase I/IIa, randomized, single-blind, placebo-controlled, multiple-ascending dose study conducted at a single site. The study plans to include up to approximately 46 evaluable subjects with Type 2 Diabetes Mellitus (HbA1c 7-11%) and Non-Alcoholic Fatty Liver disease (liver fat content > = 8%) on metformin… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- T2DM With NAFLD
- What is being tested?
- AZD4076
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- No sites listed yet
- Study dates
- 18 Jul 2016to 11 Oct 2019
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Males or females of non-child bearing potential.
- Age 18-70 years with suitable veins for cannulation or repeated venipuncture.
- BMI 23-40 kg/m2 inclusive.
- Diagnosed T2D (HbA1c 7-11%) treated with a stable dose of metformin for at least one month prior to screening.
- Hepatic steatosis of ≥8%.
Who cannot join
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- History or presence of hepatic or renal disease (with the exception of hepatic steatosis).
- Presence of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy.
- Clinically significant cardiovascular event within the last 6 months prior to screening.
- History or presence of significant neurological or psychiatric disease/mental illness (as assessed using the C-SSRS).
- History of malignancy within the last 5 years, excluding successful treatment of basal cell skin carcinoma or in situ carcinoma of cervix.
Show all 34Show fewer
- Suspicion of or known Gilbert's syndrome.
- Supine systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg confirmed in the screening period.
- Changes in any current medication (initiation, dose change or cessation) that may impact the study readouts (as judged by the Investigator) within three months prior to MRI assessment of steatosis screening. The criterion does not apply to medication prescribed for occasional use.
- 10 Treatment with antidiabetics (except for metformin) during the last three months prior to screening or treatment with sulfonylurea (SU) drugs within the 4 weeks prior to screening.
- 11. Used or plan to use drugs that cause weight loss, participating in, or have participated in weight loss program within the last 3 months.
- 12. Use of anabolic steroids and systemic treatment with glucosteroids within three months prior to screening. Intra articular, topical, and inhaled steroids are permissible.
- 13. Any confirmed clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the Investigator.
- 14. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
- 15. Confirmed serum creatinine greater than the ULN. 16. A confirmed eGFR <60 calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- 17. Confirmed platelet count outside the normal range. 18. Confirmed ALT or AST greater than 1.5x ULN. 19. Confirmed total bilirubin greater than ULN 20. Any clinically significant abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead, or left ventricular hypertrophy.
- 21. Prolonged QTcF > 450 ms for males and > 470 ms for females or family history of long QT syndrome.
- 22. PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation.
- 23. PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation.
- 24. Persistent or intermittent complete bundle branch block (BBB) with QRS > 120 ms.
- 25. Known or suspected history of drug abuse within the past 5 years, as judged by the Investigator.
- 26. Smokes >10 cigarettes/day and unable to comply with the nicotine restriction during the study.
- 27. History of alcohol abuse or excessive intake of alcohol. Definition of excessive intake: an average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- 28. Positive screen for drugs of abuse at screening or admission to the unit or positive screen for alcohol at screening or on admission to the unit prior to the first administration of IMP.
- 29. History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4076.
- 30. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea), as judged by the Investigator.
- 31. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- 32. Plasma donation within one month of screening or any blood donation/blood loss > 500 mL during the 56 days prior to screening.
- 33. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within one month of the administration of IMP in this study. The period of exclusion begins one month after the final dose or one month after the last visit whichever is the longest.
- 34. Use of implants or devices that are incompatible with the MRI procedure. 35. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- 36. Involvement of any Astra Zeneca, PROFIL INSTITUTE or study site employee or their close relatives.
- 37. Judgment by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- 38. Subjects not willing to comply with the dietary requirements in the study as judged by the Investigator.
- 39. Subjects who cannot communicate reliably with the Investigator or designee. 40. Previous bone marrow transplant. 41. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
About this study
Official title: Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD4076 Following Multiple Ascending Dose Administration to T2DM Subjects With Non-Alcoholic Fatty Liver Disease
This is a phase I/IIa, randomized, single-blind, placebo-controlled, multiple-ascending dose study conducted at a single site. The study plans to include up to approximately 46 evaluable subjects with Type 2 Diabetes Mellitus (HbA1c 7-11%) and Non-Alcoholic Fatty Liver disease (liver fat content > = 8%) on metformin monotherapy.
Three initial cohorts are planned:
Read more
- Cohort 1: 6 subjects receiving AZD4076 and 4 subjects receiving placebo
- Cohort 2: 12 subjects receiving AZD4076 and 10 subjects receiving placebo
- Cohort 3: 10 subjects receiving AZD4076 and 10 subjects receiving placebo, with the possibility to add additional subjects if drop-out rates are higher than expected
Pending review by SRC, an additional 2 cohorts, each consisting of 18 evaluable subjects may be included in the study.
The primary objectives of this clinical trial are to investigate the safety and tolerability of AZD4076 following subcutaneous administration of multiple ascending doses; to assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique; and to assess the effect of AZD4076 on liver fat content using magnetic resonance imaging. Secondary objectives of this trial are to characterize multiple dose PK of AZD4076 and its longmer and shortmer metabolites and assess the time required to reach steady state and the degree of accumulation; to assess the efficacy of AZD4076 on 24-hour glucose; and to assess the effect of AZD4076 on homeostatic model assessment insulin resistant (HOMA-IR) and Matsuda index.
Read the detailed description
This is a phase I/IIa, randomized, single-blind, placebo-controlled, multiple-ascending dose study conducted at a single site. The study plans to include up to approximately 46 evaluable subjects with Type 2 Diabetes Mellitus (HbA1c 7-11%) and Non-Alcoholic Fatty Liver disease (liver fat content > = 8%) on metformin monotherapy
Three initial cohorts are planned:
- Cohort 1: 6 subjects receiving AZD4076 and 4 subjects receiving placebo
- Cohort 2: 12 subjects receiving AZD4076 and 10 subjects receiving placebo
- Cohort 3: 10 subjects receiving AZD4076 and 10 subjects receiving placebo, with the possibility to add additional subjects if drop-out rates are higher than expected.
Pending review by SRC, an additional 2 cohorts, each consisting of 18 evaluable subjects may be included in the study.
The planned study consists of a screening visit, followed by 12 subsequent study visits. There will be a total of three residential periods: (1) Loading phase of the treatment (visit 2, days -4 to 14), (2) maintenance phase of treatment (visit 6, days 42-43), and (3) 8 weeks post-first dose of study drug (visit 9, days 53-56). Dosing of study drug will take place on days 1, 3, 5, 7, and 9 in the loading phase; and on days 14, 21, 28, 35, and 42 during the maintenance phase. Following the maintenance phase, subjects will have four follow-up visits.
Study Objectives:
The primary objectives of this clinical trial are to investigate the safety and tolerability of AZD4076 following subcutaneous administration of multiple ascending doses; to assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique; and to assess the effect of AZD4076 on liver fat content using magnetic resonance imaging. Secondary objectives of this trial are to characterize multiple dose PK of AZD4076 and its longmer and shortmer metabolites and assess the time required to reach steady state and the degree of accumulation; to assess the efficacy of AZD4076 on 24-hour glucose; and to assess the effect of AZD4076 on homeostatic model assessment insulin resistant (HOMA-IR) and Matsuda index.
Study Population:
Subjects participating in this study are adult males and females of non-child bearing potential, who are 18-70 years of age, body mass index 23-40 kg/m2, diagnosed with T2DM who are inadequately controlled (HbA1C 7-11%) on a stable metformin regimen, and who have hepatic steatosis (defined as liver fat content of >=8% per MRI).
Duration of treatment:
The screening visit will occur within 42 days prior to the administration of the study drug. Total length of the treatment period is 6 weeks. The treatment period is divided in two phases: the loading phase, in which participants will receive the study drug every other day for 9 days (Days 1, 3, 5 , 7 and 9); thereafter subjects will enter the maintenance phase, where dosing will occur once weekly for four weeks (Days 14, 21, 28, 35 and 42). To ensure safety, subjects will be followed for approximately 5 months post the last dose of study drug.
Investigational product, dosage and mode of administration:
The study will utilize two study drugs: AZD4076 and placebo. Both drugs will be administered subcutaneously in the abdomen.
Safety analysis:
The key outcomes for the safety analyses are: adverse events, vital signs, safety laboratory parameters, ECGs, telemetry; and structured neurological and physical examination, as well as injection site assessment. Pharmacodynamic parameters will be derived from data generated from the clamp procedure, MRI, HOMA, OGTT and 24-hour glucose AUC. For pharmacokinetic parameters, plasma and urine concentrations of AZD4076 and its metabolites will be measured
- Conditions
- T2DM With NAFLD
- Being tested
- AZD4076, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4076Drug
Also called Study drug
Investigational product
PlaceboDrug
Also called Control
Control
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Subjects in this arm will receive AZD4076 Receives: Drug: AZD4076 |
| Control | Placebo comparator | Subjects in this arm will receive placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety and tolerability of AZD4076 by assessing the number of participants with adverse events
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessment of blood pressure
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessment of pulse
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessment of oral temperature
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From day -2 until day 42
The safety and tolerability of AZD4076 by assessment of electrocardiogram readings
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessment of digital electrocardiogram readings
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From predose until 24 hours post-dose on days 1 and 42
The safety and tolerability AZD4076 by assessment of physical examination
Percentage of patients with abnormal physical examination
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessing the injection site
Percentage of patients with dermatological adverse events
Measured: From day 1 until day 42
The safety and tolerability of AZD4076 by assessing the number of adverse events
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessing hematology
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessing clinical chemistry
Percentage of patients with clinically significant changes in laboratory tests.
Measured: From screening until 26 weeks post first dose
The safety and tolerability of AZD4076 by assessing urinalysis
To assess the safety and tolerability of multiple ascending doses of AZD4076
Measured: From screening until 26 weeks post-first dose
Glucose infusion rate at hyperinsulinemic clamp
To assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique
Measured: Day -1 and 56 days post first dose
Reduction in liver fat content (%) per MRI
To assess the effect of AZD4076 on liver fat content using magnetic resonance imaging
Measured: Screening and 54 days post first dose
Secondary outcomes (11)
24 hour glucose area under the curve
To assess the effect of AZD4076 on 24-hour glucose.
Measured: Day -2 and day 55
HOMA-IR
To assess the effect of AZD4076 on homeostatic model assessment insulin resistant (HOMA-IR)
Measured: Day -2 and day 55
Fasting Endogenous Glucose Production
To assess the effect of AZD4076 on endogenous glucose production (EGP).
Measured: Day -1 and day 56
AUCt of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by area under the curve to time
Measured: Dosing day 1 and day 42
Matsuda Index
To assess the effect of AZD4076 on Matusda Index
Measured: Day -2 and day 55
AUC0-24 of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by area under the curve to 24 hours
Measured: Dosing day 1 and day 42
Cmax of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by peak concentration
Measured: Dosing day 1 and day 42
Tmax of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by time to peak concentration
Measured: Dosing day 1 and day 42
CLR of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by clearance
Measured: Day 1 and 42
fe% of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by fraction excreted in urine
Measured: Dosing day 1 and day 42
Ae of AZD4076 and longmer and shortmer metabolites
To characterize pharmacokinetics of AZD4076 by amount excreted in urine
Measured: Dosing day 1 and day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study start18 Jul 2016
- Primary completion11 Oct 2019
- Study completion11 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for T2DM With NAFLDStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Linda Morrow, MD, Principal investigator, ProSciento, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02826525
- Sponsor's protocol ID
- D5590C00002
- Status last verified
- Mar 2021
- First submitted
- 29 Jun 2016
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD4076 Following Multiple Ascending Dose Administration to T2DM Subjects With Non-Alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT02826525
- Acronym / sponsor ID
- D5590C00002
- Conditions
- T2DM With NAFLD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 18 Jul 2016 (actual)
- Primary completion
- 11 Oct 2019 (actual)
- Study completion
- 11 Oct 2019 (actual)
- First posted
- 11 Jul 2016 (estimated)
- 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 is a phase I/IIa, randomized, single-blind, placebo-controlled, multiple-ascending dose study conducted at a single site. The study plans to include up to approximately 46 evaluable subjects with Type 2 Diabetes Mellitus (HbA1c 7-11%) and Non-Alcoholic Fatty Liver disease (liver fat content > = 8%) on metformin monotherapy.
Three initial cohorts are planned:
- Cohort 1: 6 subjects receiving AZD4076 and 4 subjects receiving placebo
- Cohort 2: 12 subjects receiving AZD4076 and 10 subjects receiving placebo
- Cohort 3: 10 subjects receiving AZD4076 and 10 subjects receiving placebo, with the possibility to add additional subjects if drop-out rates are higher than expected
Pending review by SRC, an additional 2 cohorts, each consisting of 18 evaluable subjects may be included in the study.
The primary objectives of this clinical trial are to investigate the safety and tolerability of AZD4076 following subcutaneous administration of multiple ascending doses; to assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique; and to assess the effect of AZD4076 on liver fat content using magnetic resonance imaging. Secondary objectives of this trial are to characterize multiple dose PK of AZD4076 and its longmer and shortmer metabolites and assess the time required to reach steady state and the degree of accumulation; to assess the efficacy of AZD4076 on 24-hour glucose; and to assess the effect of AZD4076 on homeostatic model assessment insulin resistant (HOMA-IR) and Matsuda index.
Detailed description
This is a phase I/IIa, randomized, single-blind, placebo-controlled, multiple-ascending dose study conducted at a single site. The study plans to include up to approximately 46 evaluable subjects with Type 2 Diabetes Mellitus (HbA1c 7-11%) and Non-Alcoholic Fatty Liver disease (liver fat content > = 8%) on metformin monotherapy
Three initial cohorts are planned:
- Cohort 1: 6 subjects receiving AZD4076 and 4 subjects receiving placebo
- Cohort 2: 12 subjects receiving AZD4076 and 10 subjects receiving placebo
- Cohort 3: 10 subjects receiving AZD4076 and 10 subjects receiving placebo, with the possibility to add additional subjects if drop-out rates are higher than expected.
Pending review by SRC, an additional 2 cohorts, each consisting of 18 evaluable subjects may be included in the study.
The planned study consists of a screening visit, followed by 12 subsequent study visits. There will be a total of three residential periods: (1) Loading phase of the treatment (visit 2, days -4 to 14), (2) maintenance phase of treatment (visit 6, days 42-43), and (3) 8 weeks post-first dose of study drug (visit 9, days 53-56). Dosing of study drug will take place on days 1, 3, 5, 7, and 9 in the loading phase; and on days 14, 21, 28, 35, and 42 during the maintenance phase. Following the maintenance phase, subjects will have four follow-up visits.
Study Objectives:
The primary objectives of this clinical trial are to investigate the safety and tolerability of AZD4076 following subcutaneous administration of multiple ascending doses; to assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique; and to assess the effect of AZD4076 on liver fat content using magnetic resonance imaging. Secondary objectives of this trial are to characterize multiple dose PK of AZD4076 and its longmer and shortmer metabolites and assess the time required to reach steady state and the degree of accumulation; to assess the efficacy of AZD4076 on 24-hour glucose; and to assess the effect of AZD4076 on homeostatic model assessment insulin resistant (HOMA-IR) and Matsuda index.
Study Population:
Subjects participating in this study are adult males and females of non-child bearing potential, who are 18-70 years of age, body mass index 23-40 kg/m2, diagnosed with T2DM who are inadequately controlled (HbA1C 7-11%) on a stable metformin regimen, and who have hepatic steatosis (defined as liver fat content of >=8% per MRI).
Duration of treatment:
The screening visit will occur within 42 days prior to the administration of the study drug. Total length of the treatment period is 6 weeks. The treatment period is divided in two phases: the loading phase, in which participants will receive the study drug every other day for 9 days (Days 1, 3, 5 , 7 and 9); thereafter subjects will enter the maintenance phase, where dosing will occur once weekly for four weeks (Days 14, 21, 28, 35 and 42). To ensure safety, subjects will be followed for approximately 5 months post the last dose of study drug.
Investigational product, dosage and mode of administration:
The study will utilize two study drugs: AZD4076 and placebo. Both drugs will be administered subcutaneously in the abdomen.
Safety analysis:
The key outcomes for the safety analyses are: adverse events, vital signs, safety laboratory parameters, ECGs, telemetry; and structured neurological and physical examination, as well as injection site assessment. Pharmacodynamic parameters will be derived from data generated from the clamp procedure, MRI, HOMA, OGTT and 24-hour glucose AUC. For pharmacokinetic parameters, plasma and urine concentrations of AZD4076 and its metabolites will be measured
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: AZD4076Subjects in this arm will receive AZD4076 |
| Control | Placebo comparator | Drug: PlaceboSubjects in this arm will receive placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Males or females of non-child bearing potential.
- Age 18-70 years with suitable veins for cannulation or repeated venipuncture.
- BMI 23-40 kg/m2 inclusive.
- Diagnosed T2D (HbA1c 7-11%) treated with a stable dose of metformin for at least one month prior to screening.
Key exclusion criteria (34 listed)
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- History or presence of hepatic or renal disease (with the exception of hepatic steatosis).
- Presence of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy.
- Clinically significant cardiovascular event within the last 6 months prior to screening.
- History or presence of significant neurological or psychiatric disease/mental illness (as assessed using the C-SSRS).
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 |
|---|---|---|
| AZD4076Also: Study drugInvestigational product | Drug | Treatment |
| PlaceboAlso: ControlControl | Drug | Control |
Primary outcome
The safety and tolerability of AZD4076 by assessing the number of participants with adverse events
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessment of blood pressure
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessment of pulse
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessment of oral temperature
Time frame: From day -2 until day 42
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessment of electrocardiogram readings
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessment of digital electrocardiogram readings
Time frame: From predose until 24 hours post-dose on days 1 and 42
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability AZD4076 by assessment of physical examination
Time frame: From screening until 26 weeks post first dose
Percentage of patients with abnormal physical examination
The safety and tolerability of AZD4076 by assessing the injection site
Time frame: From day 1 until day 42
Percentage of patients with dermatological adverse events
The safety and tolerability of AZD4076 by assessing the number of adverse events
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessing hematology
Time frame: From screening until 26 weeks post first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
The safety and tolerability of AZD4076 by assessing clinical chemistry
Time frame: From screening until 26 weeks post first dose
Percentage of patients with clinically significant changes in laboratory tests.
The safety and tolerability of AZD4076 by assessing urinalysis
Time frame: From screening until 26 weeks post-first dose
To assess the safety and tolerability of multiple ascending doses of AZD4076
Glucose infusion rate at hyperinsulinemic clamp
Time frame: Day -1 and 56 days post first dose
To assess the effect of AZD4076 on whole body insulin sensitivity using hyperinsulinemic euglycemic clamp with tracer technique
Reduction in liver fat content (%) per MRI
Time frame: Screening and 54 days post first dose
To assess the effect of AZD4076 on liver fat content using magnetic resonance imaging
11 secondary outcomes
24 hour glucose area under the curve
Time frame: Day -2 and day 55
HOMA-IR
Time frame: Day -2 and day 55
Fasting Endogenous Glucose Production
Time frame: Day -1 and day 56
AUCt of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
Matsuda Index
Time frame: Day -2 and day 55
AUC0-24 of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
Cmax of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
Tmax of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
CLR of AZD4076 and longmer and shortmer metabolites
Time frame: Day 1 and 42
fe% of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
Ae of AZD4076 and longmer and shortmer metabolites
Time frame: Dosing day 1 and day 42
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
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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.
Linda Morrow, MD principal investigator
ProSciento, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD4076 in people with T2DM With NAFLD, run by AstraZeneca.
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 6 inclusion and 34 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: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The safety and tolerability of AZD4076 by assessing the number of participants with adverse events (time frame: From screening until 26 weeks post first dose). The study lists 14 primary outcomes in all. 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 1 Apr 2021.