Clinical trial NCT06703658: A Study to Investigate Multiple Ascending Doses of AZD5004 in Healthy Japanese Participants and Participants With Type 2 Diabetes Mellitus
Official title: A Phase I, Randomised, Single-blind, Placebo-controlled, Single and Repeated Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5004 in Healthy Japanese Participants and With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Type 2 Diabetes
Keywords: Obesity
Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-11-25
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From screening (Day -28) to last follow up visit (Day 8)
measure: PartB: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From screening (Day -28) to last follow up visit (Day 119 )
Secondary outcomes:
measure: PartB: AUC0-4 for glucose, insulin and C-peptide for MMTT
timeFrame: From Day 1 to Day 105
measure: PartB: Absolute change from baseline to Day 105 in fasting plasma glucose
timeFrame: From Day 1 to Day 105
measure: PartB: % change from baseline to Day 105 in HOMA-IR
timeFrame: From Day 1 to Day 105
measure: PartB: The proportion of time in hyperglycaemia /hypoglycaemia over the last 7-day intervals at each dose level in CGM
timeFrame: From Day 1 to Day 106
measure: PartB: % change from baseline to Day 105 in body weight (kg)
timeFrame: From Day 1 to Day 105
measure: PartB: % change from baseline to Day 105 in waist circumference (cm)
timeFrame: From Day 1 to Day 105
measure: PartA: Area under the Plasma Concentration vs. Time Curve(AUC0-24)
timeFrame: From Day 1 to Day 6
measure: 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)
timeFrame: From Day 1 to Day 6
measure: PartA: Area under the Plasma Concentration vs. Time Curve from Zero to Infinity(AUC0-inf)
timeFrame: From Day 1 to Day 6
measure: PartA: Maximum Observed Plasma Concentration(Cmax)
timeFrame: From Day 1 to Day 6
measure: PartA: Plasma Concentration at 24 Hours Post-Dose(C24h)
timeFrame: From Day 1 to Day 6
measure: PartA: Time of Occurrence of Maximum Plasma Concentration(tmax)
timeFrame: From Day 1 to Day 6
measure: PartA: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)
timeFrame: From Day 1 to Day 6
measure: PartA: Half-Life(t1/2)
timeFrame: From Day 1 to Day 6
measure: PartA: Last measurable Non-Zero Concentration(Clast)
timeFrame: From Day 1 to Day 6
measure: PartA: Last measurable Non-Zero ConcentrationTime to Last Detectable Concentration(tlast)
timeFrame: From Day 1 to Day 6
measure: PartA: Apparent Oral Clearance(CL/F)
timeFrame: From Day 1 to Day 6
measure: PartA: Cumulative Urinary Excretion(Ae)
timeFrame: From Day 1 to Day 6
measure: PartA: Clearance(CLR)
timeFrame: From Day 1 to Day 6
measure: PartB: Area under the Plasma Concentration vs. Time Curve(AUC0-24)
timeFrame: Day 1
measure: PartB: Maximum Observed Plasma Concentration(Cmax)
timeFrame: Day 1, Day 49, Day 63, Day 77, Day91, Day105
measure: PartB: Plasma Concentration at 24 Hours Post-Dose(C24h)
timeFrame: Day 1
measure: PartB: Time of Occurrence of Maximum Plasma Concentration(tmax)
timeFrame: Day 1, Day 49, Day 63, Day 77, Day91, Day105
measure: PartB: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)
timeFrame: Day 1
measure: PartB: Area under the Plasma Concentration vs. Time Curve over the Dosing Interval(AUC0-τ)
timeFrame: Day 49, Day 63, Day 77, Day 91, Day 105
measure: PartB: Observed Concentration at the End of the Dosing Interval(Cτ)
timeFrame: Day 49, Day 63, Day 77, Day 91, Day 105
measure: PartB: Half-Life(t1/2)
timeFrame: Day 49, Day 63, Day 77, Day 91, Day 105
measure: PartB: Apparent Oral Clearance(CL/F)
timeFrame: Day 49, Day 63, Day 77, Day 91, Day 105
measure: PartB: Cumulative Urinary Excretion(Ae)
timeFrame: Day 105
measure: PartB: Clearance(CLR)
timeFrame: Day 105
Other outcomes:
Locations:
city: Osaka-shi
country: Japan
facility: Research Site
Study officials:
References: