Healthy Participants, Type 2 Diabetes
Conditions
Keywords
Obesity, Type 2 Diabetes
Brief summary
This Phase I study will gather important information on the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5004 in both healthy Japanese participants and Japanese participants with T2DM.
Detailed description
This is a placebo-controlled study to assess the safety, efficacy, tolerability, and PK of single and repeated dosing of AZD5004 compared with placebo. Participants who are eligible according to the inclusion/exclusion criteria will be randomized to receive AZD5004 or matching placebo. The study will comprise: 1. A Screening Period of maximum 28 days. 2. A Treatment Period of 1 day(Part A) or 105 days (Part B). 3. A final Follow-up Visit approximately 7 days(Part A) or 14 days(Part B) after the last study intervention administration.
Interventions
DRUGAZD5004(Part A)
Single dose of AZD5004 oral on Day1
DRUGPlacebo(Part A)
Single dose of placebo oral on Day1
DRUGAZD5004(Part B)
AZD5004 will be administered as an oral tablet once daily.
DRUGPlacebo(Part B)
Placebo will be administered as an oral tablet once daily.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Japanese men or women, and 18-65 years of age inclusive, at the time of signing the informed consent. Inclusion Criteria for Part A: * HbA1c ≤ 6.0%. * Body weight ≥ 50.0 kg and BMI within the range 18.0-32.0 kg/m2. Inclusion Criteria for Part B: * HbA1c ≥ 6.5% and ≤ 10.5%. * Not on any other diabetic medications. * Body weight ≥ 60.0 kg and BMI within the range 24.0-35.0 kg/m2
Exclusion criteria
* Has a clinically relevant acute or chronic medical condition or disease. * History of acute pancreatitis and chronic pancreatitis, gallstones. * Abnormal renal function. * Known clinically significant gastric emptying abnormality * Significant hepatic disease. * Uncontrolled thyroid disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs) | From screening (Day -28) to last follow up visit (Day 8) | To assess the safety and tolerability of AZD5004 following single oral doses in healthy participants. |
| PartB: Number of participants with adverse events (AEs) and serious adverse events (SAEs) | From screening (Day -28) to last follow up visit (Day 119 ) | To assess the safety and tolerability of AZD5004 following multiple oral ascending doses in participants with T2DM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PartB: Absolute change from baseline to Day 105 in fasting plasma glucose | From Day 1 to Day 105 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: % change from baseline to Day 105 in HOMA-IR | From Day 1 to Day 105 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: The proportion of time in hyperglycaemia /hypoglycaemia over the last 7-day intervals at each dose level in CGM | From Day 1 to Day 106 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: % change from baseline to Day 105 in body weight (kg) | From Day 1 to Day 105 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: % change from baseline to Day 105 in waist circumference (cm) | From Day 1 to Day 105 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartA: Area under the Plasma Concentration vs. Time Curve(AUC0-24) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Area under the Plasma Concentration vs. Time Curve from Zero until the Time of the Last Concentration above the Limit of Quantification(AUC0-tlast) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Area under the Plasma Concentration vs. Time Curve from Zero to Infinity(AUC0-inf) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Plasma Concentration at 24 Hours Post-Dose(C24h) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Time of Occurrence of Maximum Plasma Concentration(tmax) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Half-Life(t1/2) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Last measurable Non-Zero Concentration(Clast) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Last measurable Non-Zero ConcentrationTime to Last Detectable Concentration(tlast) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Maximum Observed Plasma Concentration(Cmax) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Cumulative Urinary Excretion(Ae) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartA: Clearance(CLR) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartB: Area under the Plasma Concentration vs. Time Curve(AUC0-24) | Day 1 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Maximum Observed Plasma Concentration(Cmax) | Day 1, Day 49, Day 63, Day 77, Day91, Day105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Plasma Concentration at 24 Hours Post-Dose(C24h) | Day 1 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Time of Occurrence of Maximum Plasma Concentration(tmax) | Day 1, Day 49, Day 63, Day 77, Day91, Day105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag) | Day 1 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Area under the Plasma Concentration vs. Time Curve over the Dosing Interval(AUC0-τ) | Day 49, Day 63, Day 77, Day 91, Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Observed Concentration at the End of the Dosing Interval(Cτ) | Day 49, Day 63, Day 77, Day 91, Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Half-Life(t1/2) | Day 49, Day 63, Day 77, Day 91, Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Apparent Oral Clearance(CL/F) | Day 49, Day 63, Day 77, Day 91, Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Cumulative Urinary Excretion(Ae) | Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartB: Clearance(CLR) | Day 105 | To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD |
| PartA: Apparent Oral Clearance(CL/F) | From Day 1 to Day 6 | To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD |
| PartB: AUC0-4 for glucose, insulin and C-peptide for MMTT | From Day 1 to Day 105 | To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD |
Countries
Japan
Outcome results
None listed