Phase 1
Completed N=81
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus
Source: ClinicalTrials.gov NCT02445911 ↗Enrolled (actual)
81
Serious AEs
1.2%
Results posted
Oct 2019
Primary outcomePrimary: Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo — -3.28; -3.93; 0.67; 3.17 mg/dL milligrams per deciliters
Summary
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo |
-3.28; -3.93; 0.67; 3.17 | — |
| PRIMARY Number of Participants With One or More Treatment-Emergent Adverse Events |
12; 12; 11; 14 | — |
| SECONDARY Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) |
.0043; .003; .005; -.0012 | — |
| SECONDARY Change From Baseline in the Insulin Sensitivity Index (ISI) |
.0043; -.0585; 0.145; -0.112 | — |
| SECONDARY Change From Baseline in Beta Cell Function |
0.00098; 0.012; 0.0535; 0.0027 | — |
| SECONDARY Change From Baseline in Disposition Index |
0.022; 0.023; 0.084; 0.008 | — |
| SECONDARY Change From Baseline in the Hepatic Insulin Resistance Index |
99.51; 255.53; 93.17; 56.90 | — |
| SECONDARY Change From Baseline in 7-point Average Blood Glucose |
-5.04; 0.35; -2.61; 4.44 | — |
| SECONDARY Change From Baseline in Postprandial Glucose |
-72.23; -0.086; -35.60; 58.61 | — |
| SECONDARY Change From Baseline in HbA1c |
-0.185; 0.025; -0.315; -0.0333 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24) |
14372.2; 29011.2; 140990.4 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) |
747.56; 1484.74; 7204.70 | — |
| SECONDARY Time of the Maximum Measured Plasma Concentration (Tmax) |
4.60; 5.05; 9.42 | — |
| SECONDARY Area Under the Plasma Concentration Versus Time Curve (AUCtau) |
76863.5; 25754.9; 150681.0 | — |
| SECONDARY Maximum Observed Plasma Concentration at Steady-state (Cmax_ss) |
657.82; 1164.65; 7221.37 | — |
| SECONDARY Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss) |
5.10; 5.43; 3.83 | — |
| SECONDARY Apparent Terminal Elimination Half-life (t1/2) |
201.095; 184.386; 178.018 | — |
| SECONDARY Accumulation Index (AI) |
1.97; 9.37; 12.01 | — |
Eligibility Criteria
Inclusion Criteria
- Have a diagnosis of Type 2 Diabetes Mellitus (T2DM)
- Be an adult between the ages of 18 (19 for Lincoln site) and 70 years
- Female participants must be of non-childbearing potential, and must be either 1) postmenopausal with amenorrhea for at least 1 year prior to the first dose and Follicle Stimulating Hormone (FSH) serum levels consistent with postmenopausal status, or 2) have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
- hysteroscopic sterilization
- bilateral tubal ligation or bilateral salpingectomy
- hysterectomy
- bilateral oophorectomy
- Non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 100 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dosing. A male who has been vasectomized less than 4 months prior to first dosing must follow the same restrictions as a non-vasectomized male)
- Males must agree to not donate sperm during the study and for 100 days following the last dose
- Have an HbA1c value between 7.0-10.0%
- Be on a stable treatment regimen of metformin, with or without diet/exercise, for at least 8 weeks
- Weigh 60 kilograms (kg) or more at screening and have a body mass index (BMI) greater than or equal to (≥) 25.0 and less than or equal to (≤) 40.0 kilograms/meters squared (kg/m2)
- Have laboratory test results within the normal range for T2DM population, or with abnormalities deemed clinically insignificant. Urine protein levels must be within normal limits
- Absence of active diabetic retinopathy (Stage 2 or greater by the International Clinical Disease Severity Scale for Diabetic Retinopathy)
- Are willing to comply with specific dietary restrictions (that is, [i] able to fast overnight for at least 8-12 hours on several days and [ii] able to consume the standard meals provided during specified confinement days)
- Have given written consent to allow collection of samples for Peripheral Blood Mononuclear Cells (PBMC) analysis and for possible biomarkers/safety analysis
- Have given written informed consent approved by the institutional review board (IRB) governing the site
Exclusion Criteria
- Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- Participated (defined as the last dose of study drug) within 30 days prior to dosing in a clinical trial involving an investigational product or non-approved use of a drug with a short half-life or within 5 half-lives of an investigational product with a half-life longer than 6 days
- - Have a (QTcF) greater than (>) 450 milliseconds (msec), or clinical significant hypokalemia, a family history of long QT syndrome or any abnormality in the 12-lead Electrocardiogram (ECG)
- Abnormal blood pressure (sitting) defined as diastolic blood pressure > 95 or less than ( 160 or 1 episode of documented severe hypoglycemia within last 6 months or are currently diagnosed as having hypoglycemia unawareness
- Have any of the following clinical laboratory test results:
- estimated glomerular filtration rate (eGFR) 1.5 times (x) the upper limit of normal (ULN)
- triglycerides (TG) > 500 milligrams/deciliter (mg/dL)
- Have used insulin or other glycemic control medications, except metformin, for diabetic control within 3 months
- Intend to use non-steroidal anti-inflammatory drugs (except aspirin) and drugs known to prolong QT interval, herbal products, or vitamin supplements that change glucose levels. The following medications are allowed for participants:
- drugs for treatment of hypertension or lipid disorders (except bile acid resins, niacin or fish oils), platelet inhibitors, and on stable dose for 1
Data sourced from ClinicalTrials.gov (NCT02445911). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.