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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
35
Single dose of AZD5004 oral on Day1
Single dose of placebo oral on Day1
AZD5004 will be administered as an oral tablet once daily.
Research Site
Osaka, Japan
PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
To assess the safety and tolerability of AZD5004 following single oral doses in healthy participants.
Time frame: From screening (Day -28) to last follow up visit (Day 8)
PartB: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
To assess the safety and tolerability of AZD5004 following multiple oral ascending doses in participants with T2DM.
Time frame: From screening (Day -28) to last follow up visit (Day 119 )
PartB: AUC0-4 for glucose, insulin and C-peptide for MMTT
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 105
PartB: Absolute change from baseline to Day 105 in fasting plasma glucose
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 105
PartB: % change from baseline to Day 105 in HOMA-IR
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 105
PartB: The proportion of time in hyperglycaemia /hypoglycaemia over the last 7-day intervals at each dose level in CGM
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 106
PartB: % change from baseline to Day 105 in body weight (kg)
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Placebo will be administered as an oral tablet once daily.
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 105
PartB: % change from baseline to Day 105 in waist circumference (cm)
To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: From Day 1 to Day 105
PartA: Area under the Plasma Concentration vs. Time Curve(AUC0-24)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
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)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Area under the Plasma Concentration vs. Time Curve from Zero to Infinity(AUC0-inf)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Maximum Observed Plasma Concentration(Cmax)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Plasma Concentration at 24 Hours Post-Dose(C24h)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Time of Occurrence of Maximum Plasma Concentration(tmax)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Half-Life(t1/2)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Last measurable Non-Zero Concentration(Clast)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Last measurable Non-Zero ConcentrationTime to Last Detectable Concentration(tlast)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Apparent Oral Clearance(CL/F)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Cumulative Urinary Excretion(Ae)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartA: Clearance(CLR)
To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD
Time frame: From Day 1 to Day 6
PartB: Area under the Plasma Concentration vs. Time Curve(AUC0-24)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 1
PartB: Maximum Observed Plasma Concentration(Cmax)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 1, Day 49, Day 63, Day 77, Day91, Day105
PartB: Plasma Concentration at 24 Hours Post-Dose(C24h)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 1
PartB: Time of Occurrence of Maximum Plasma Concentration(tmax)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 1, Day 49, Day 63, Day 77, Day91, Day105
PartB: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 1
PartB: Area under the Plasma Concentration vs. Time Curve over the Dosing Interval(AUC0-τ)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Observed Concentration at the End of the Dosing Interval(Cτ)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Half-Life(t1/2)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Apparent Oral Clearance(CL/F)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Cumulative Urinary Excretion(Ae)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 105
PartB: Clearance(CLR)
To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD
Time frame: Day 105