Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
Overweight, Obese, Fructose, siRNA, HbA1C, Insulin, Glucose
Brief summary
To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-KHK and to evaluate the safety, tolerability, efficacy, PK and PD of multiple doses of KHK.
Interventions
DRUGALN-KHK
ALN-KHK will be administered by subcutaneous (SC) injection.
DRUGPlacebo
Placebo will be administered by subcutaneous (SC) injection.
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
The single ascending dose part of this study (Part A) will have a sequential interventional study model. The multi-dose part of this study (Part B) will have a parallel interventional study model and will begin after the completion of Part A.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Stable euthyroid status (no known changes in thyroid function; stable hormone replacement for at least 4 months) at screening * Part A: body mass index (BMI) ≥27 kg/m\^2 and ≤34.9 kg/m\^2 * Part B: BMI ≥30 kg/m\^2 to ≤39.9 kg/m\^2, confirmed diagnosis of T2DM, and an HbA1c ≥7.5% to \<10% * Part B: Confirmed T2DM diagnosis
Exclusion criteria
* Parts A and B: has received an investigational agent within the last 30 days * Part A: History of Type 1 or Type 2 diabetes * Part B: History of Type 1 diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Frequency of Adverse Events | Up to 9 Months |
| Part B: Frequency of Adverse Events | Up to 12 Months |
Secondary
| Measure | Time frame |
|---|---|
| Part A: Time to Maximum Observed Plasma Concentration (Tmax) of ALN-KHK and Potential Major Metabolite(s) | Up to 2 Days following dosing on Day 1 |
| Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s) | Postdose on Day 1 |
| Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test | Baseline up to Month 6 |
| Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test | Baseline up to Month 6 |
| Part A: Percent Change from Baseline in Circulating Fibroblast Growth Factor 21 (FGF21) in Response to a Fructose Tolerance Test | Baseline up to Month 6 |
| Part A: Area Under the Concentration-time Curve (AUC) of ALN-KHK and Potential Major Metabolite(s) | Up to 2 Days following dosing on Day 1 |
| Parts A and B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test | Part A: Screening up to Month 3; Part B: Month 4 |
| Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Month 4 |
| Parts A and B: Glucose and Insulin AUC in response to Tolerance Test | Part A: Screening up to Month 3; Part B: Month 4 |
| Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s) | Day 1 and Month 3 |
| Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months | Baseline and Month 6 |
| Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s) | Up to 2 Days following dosing on Day 1 |
Countries
Canada, United States
Outcome results
None listed