A Study to Investigate Multiple Ascending Doses of AZD5004 in Healthy Japanese Participants and Participants With Type 2 Diabetes Mellitus
- Conditions
- Healthy ParticipantsType 2 Diabetes
- Interventions
- Drug: AZD5004(Part A)Drug: Placebo(Part A)Drug: AZD5004(Part B)Drug: Placebo(Part B)
- Registration Number
- NCT06703658
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A-AZD5004 AZD5004(Part A) Participants will receive AZD5004 orally. Part A-Placebo Placebo(Part A) Participants will receive matching Placebo orally. Part B-AZD5004 AZD5004(Part B) Participants will receive AZD5004 orally. Part B-Placebo Placebo(Part B) Participants will receive matching Placebo orally.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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: 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: 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: 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
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
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Trial Locations
- Locations (1)
Research Site
🇯🇵Osaka-shi, Japan