Diabetes Mellitus, Type 2
Conditions
Brief summary
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days.
Interventions
DRUGKQ-791
Capsules administered orally
DRUGPlacebo
Capsules administered orally
Sponsors
Kaneq Bioscience Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 (\<) 50 millimeter of mercury (mmHg) and/or systolic blood pressure \> 160 or \< 90 mmHg * Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs * Show evidence of regular use of known drugs of abuse and/or positive findings on urinary drug screening * Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C and/or positive results at screening for the respective antibodies for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) * Have anemia that would interfere with the trial or have donated ≥500 mL of blood within 56 days before the first dose or have donated plasma within 7 days before the first dose or provided any blood donation within last 30 days * Have an average weekly alcohol intake that exceeds 14 units per week (males) and 7 units per week (females) \[1 unit = 12 ounces (oz) or 360 mL of beer, 5 oz or 150 mL of wine, or 1.5 oz or 45 mL of distilled spirits\] or are unwilling to stop alcohol consumption 48 hours prior to the first dosing and throughout the study * Consume more than 10 cigarettes per day or the equivalent or are unable or unwilling to adhere to restricted smoking policies * Have had \>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) \< 60 mL/min/1.73 m2 (impaired renal function) * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 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 12 weeks prior to first dose * thyroid replacement therapy, proton pump inhibitors, antidepressants, antihistamines, regularly taken over-the-counter (OTC) and anti-emetics that do not cause a corrected QT interval (QTc) prolongation, provided such drugs are not specifically excluded * hormonal replacement therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo | Baseline to Day 29 | Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo. |
| Number of Participants With One or More Treatment-Emergent Adverse Events | Baseline to Day 29 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal Elimination Half-life (t1/2) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29 | — |
| Area Under the Plasma Concentration Versus Time Curve (AUCtau) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29 | — |
| Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) | Baseline to Day 29 | QUICKI = 1/(log FPG + log FPI) where FPG = fasting plasma glucose (mg/dL); FPI = fasting plasma insulin (estimated based on fasting serum insulin; (μIU/mL)). Lower numbers reflect greater insulin resistance. |
| Change From Baseline in the Insulin Sensitivity Index (ISI) | Baseline to Day 29 | Insulin sensitivity index (ISI) composite using Matsuda's whole body insulin sensitivity, ISI \[composite\] = 10000/√\[(FPG x FPI)x(Mean Glucose 0-120min in MMTT x Mean Insulin 0-120 min in MMTT)\] where MMTT is a mixed meal tolerance test, Hour 0=just prior dosing. Lower values indicate greater insulin resistance. |
| Change From Baseline in Beta Cell Function | Baseline to Day 29 | Evaluated as beta index = (Insulin Area Under the Effect Curve (AUEC) in MMTT/Glucose AUEC in MMTT) |
| Change From Baseline in Disposition Index | Baseline to Day 29 | Disposition Index evaluated as beta index x ISI \[composite\]. Lower values of the disposition index suggests loss of function of beta cells. |
| Change From Baseline in the Hepatic Insulin Resistance Index | Baseline to Day 29 | Hepatic Insulin Resistance Index will be evaluated as Glucose AUEC from zero to 30 minutes (AUEC0-30min) in MMTT x Insulin AUEC0-30 min in MMTT |
| Maximum Observed Plasma Concentration at Steady-state (Cmax_ss) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29 | — |
| Change From Baseline in Postprandial Glucose | Baseline to Day 29 | — |
| Change From Baseline in HbA1c | Baseline to Day 29 | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose | — |
| Time of the Maximum Measured Plasma Concentration (Tmax) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose | — |
| Accumulation Index (AI) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29 | Based on AUC (RacAUC), where RacAUC is the ratio of AUC during a dosing interval following the last dose over the loading dose (first dose) |
| Change From Baseline in 7-point Average Blood Glucose | Baseline to Day 29 | The 7-points measured were just prior to each meal and 90 minutes after the start of the meal and approximately bedtime. |
| Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss) | Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KQ-791 Dose 1 Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally | 20 |
| KQ-791 Dose 2 Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally | 20 |
| KQ-791 Dose 3 Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally | 21 |
| Placebo Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally | 20 |
| Total | 81 |
Baseline characteristics
| Characteristic | KQ-791 Dose 1 | KQ-791 Dose 2 | KQ-791 Dose 3 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 1 Participants | 4 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 14 Participants | 20 Participants | 16 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 19 Participants | 17 Participants | 16 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 18 Participants | 19 Participants | 15 Participants | 69 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 21 participants | 20 participants | 81 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 10 Participants | 10 Participants | 42 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 11 Participants | 10 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 20 | 12 / 20 | 11 / 21 | 14 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 21 | 1 / 20 |
Outcome results
Primary
Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo
Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo.
Time frame: Baseline to Day 29
Population: Pharmacodynamic (PD) population incudes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo | -3.28 mg/dL milligrams per deciliters | Standard Deviation 22.99 |
| KQ-791 Dose 2 | Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo | -3.93 mg/dL milligrams per deciliters | Standard Deviation 30.63 |
| KQ-791 Dose 3 | Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo | 0.67 mg/dL milligrams per deciliters | Standard Deviation 30.82 |
| Placebo | Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo | 3.17 mg/dL milligrams per deciliters | Standard Deviation 23.17 |
95% CI: [-23.75, 10.18]
95% CI: [-19.65, 13.72]
95% CI: [-21.97, 11.88]
Primary
Number of Participants With One or More Treatment-Emergent Adverse Events
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KQ-791 Dose 1 | Number of Participants With One or More Treatment-Emergent Adverse Events | 12 participants |
| KQ-791 Dose 2 | Number of Participants With One or More Treatment-Emergent Adverse Events | 12 participants |
| KQ-791 Dose 3 | Number of Participants With One or More Treatment-Emergent Adverse Events | 11 participants |
| Placebo | Number of Participants With One or More Treatment-Emergent Adverse Events | 14 participants |
Secondary
Accumulation Index (AI)
Based on AUC (RacAUC), where RacAUC is the ratio of AUC during a dosing interval following the last dose over the loading dose (first dose)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Accumulation Index (AI) | 1.97 1/h | Standard Deviation 0.537 |
| KQ-791 Dose 2 | Accumulation Index (AI) | 9.37 1/h | Standard Deviation 4.934 |
| KQ-791 Dose 3 | Accumulation Index (AI) | 12.01 1/h | Standard Deviation 6.507 |
Secondary
Apparent Terminal Elimination Half-life (t1/2)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Apparent Terminal Elimination Half-life (t1/2) | 201.095 hours | Standard Deviation 79.378 |
| KQ-791 Dose 2 | Apparent Terminal Elimination Half-life (t1/2) | 184.386 hours | Standard Deviation 36.385 |
| KQ-791 Dose 3 | Apparent Terminal Elimination Half-life (t1/2) | 178.018 hours | Standard Deviation 28.389 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24) | 14372.2 ng*hr/mL | Standard Deviation 2882.69 |
| KQ-791 Dose 2 | Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24) | 29011.2 ng*hr/mL | Standard Deviation 6030.57 |
| KQ-791 Dose 3 | Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24) | 140990.4 ng*hr/mL | Standard Deviation 47460.96 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUCtau)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUCtau.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Area Under the Plasma Concentration Versus Time Curve (AUCtau) | 76863.5 ng*hr/mL | Standard Deviation 34469.47 |
| KQ-791 Dose 2 | Area Under the Plasma Concentration Versus Time Curve (AUCtau) | 25754.9 ng*hr/mL | Standard Deviation 13130 |
| KQ-791 Dose 3 | Area Under the Plasma Concentration Versus Time Curve (AUCtau) | 150681.0 ng*hr/mL | Standard Deviation 55372.3 |
Secondary
Change From Baseline in 7-point Average Blood Glucose
The 7-points measured were just prior to each meal and 90 minutes after the start of the meal and approximately bedtime.
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in 7-point Average Blood Glucose | -5.04 mg/dL | Standard Deviation 20.76 |
| KQ-791 Dose 2 | Change From Baseline in 7-point Average Blood Glucose | 0.35 mg/dL | Standard Deviation 35.74 |
| KQ-791 Dose 3 | Change From Baseline in 7-point Average Blood Glucose | -2.61 mg/dL | Standard Deviation 38.66 |
| Placebo | Change From Baseline in 7-point Average Blood Glucose | 4.44 mg/dL | Standard Deviation 27.91 |
Secondary
Change From Baseline in Beta Cell Function
Evaluated as beta index = (Insulin Area Under the Effect Curve (AUEC) in MMTT/Glucose AUEC in MMTT)
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in Beta Cell Function | 0.00098 (hr*μIU/mL(hr*mg/dL)) | Standard Deviation 0.0866 |
| KQ-791 Dose 2 | Change From Baseline in Beta Cell Function | 0.012 (hr*μIU/mL(hr*mg/dL)) | Standard Deviation 0.0585 |
| KQ-791 Dose 3 | Change From Baseline in Beta Cell Function | 0.0535 (hr*μIU/mL(hr*mg/dL)) | Standard Deviation 0.1099 |
| Placebo | Change From Baseline in Beta Cell Function | 0.0027 (hr*μIU/mL(hr*mg/dL)) | Standard Deviation 0.0491 |
Secondary
Change From Baseline in Disposition Index
Disposition Index evaluated as beta index x ISI \[composite\]. Lower values of the disposition index suggests loss of function of beta cells.
Time frame: Baseline to Day 29
Population: Includes all subjects who receive at least one dose of study drug and have evaluable data for disposition index.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in Disposition Index | 0.022 Index | Standard Deviation 0.128 |
| KQ-791 Dose 2 | Change From Baseline in Disposition Index | 0.023 Index | Standard Deviation 0.147 |
| KQ-791 Dose 3 | Change From Baseline in Disposition Index | 0.084 Index | Standard Deviation 0.185 |
| Placebo | Change From Baseline in Disposition Index | 0.008 Index | Standard Deviation 0.085 |
Secondary
Change From Baseline in HbA1c
Time frame: Baseline to Day 29
Population: Includes all subjects who receive at least one dose of study drug and have evaluable HbA1c data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in HbA1c | -0.185 Percentage of glycosylated hemoglobin | Standard Deviation 0.3265 |
| KQ-791 Dose 2 | Change From Baseline in HbA1c | 0.025 Percentage of glycosylated hemoglobin | Standard Deviation 0.4303 |
| KQ-791 Dose 3 | Change From Baseline in HbA1c | -0.315 Percentage of glycosylated hemoglobin | Standard Deviation 0.5174 |
| Placebo | Change From Baseline in HbA1c | -0.0333 Percentage of glycosylated hemoglobin | Standard Deviation 0.3343 |
Secondary
Change From Baseline in Postprandial Glucose
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in Postprandial Glucose | -72.23 hr*mg/dL | Standard Deviation 281.62 |
| KQ-791 Dose 2 | Change From Baseline in Postprandial Glucose | -0.086 hr*mg/dL | Standard Deviation 484.712 |
| KQ-791 Dose 3 | Change From Baseline in Postprandial Glucose | -35.60 hr*mg/dL | Standard Deviation 524.57 |
| Placebo | Change From Baseline in Postprandial Glucose | 58.61 hr*mg/dL | Standard Deviation 381.88 |
Secondary
Change From Baseline in the Hepatic Insulin Resistance Index
Hepatic Insulin Resistance Index will be evaluated as Glucose AUEC from zero to 30 minutes (AUEC0-30min) in MMTT x Insulin AUEC0-30 min in MMTT
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in the Hepatic Insulin Resistance Index | 99.51 (hr*mg/dL)*(hr*μUI/mL) | Standard Deviation 495.81 |
| KQ-791 Dose 2 | Change From Baseline in the Hepatic Insulin Resistance Index | 255.53 (hr*mg/dL)*(hr*μUI/mL) | Standard Deviation 484.27 |
| KQ-791 Dose 3 | Change From Baseline in the Hepatic Insulin Resistance Index | 93.17 (hr*mg/dL)*(hr*μUI/mL) | Standard Deviation 462.25 |
| Placebo | Change From Baseline in the Hepatic Insulin Resistance Index | 56.90 (hr*mg/dL)*(hr*μUI/mL) | Standard Deviation 482.72 |
Secondary
Change From Baseline in the Insulin Sensitivity Index (ISI)
Insulin sensitivity index (ISI) composite using Matsuda's whole body insulin sensitivity, ISI \[composite\] = 10000/√\[(FPG x FPI)x(Mean Glucose 0-120min in MMTT x Mean Insulin 0-120 min in MMTT)\] where MMTT is a mixed meal tolerance test, Hour 0=just prior dosing. Lower values indicate greater insulin resistance.
Time frame: Baseline to Day 29
Population: Includes all subjects who receive at least one dose of study drug and have evaluable ISI data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in the Insulin Sensitivity Index (ISI) | .0043 units on a scale | Standard Deviation 0.7345 |
| KQ-791 Dose 2 | Change From Baseline in the Insulin Sensitivity Index (ISI) | -.0585 units on a scale | Standard Deviation 0.586 |
| KQ-791 Dose 3 | Change From Baseline in the Insulin Sensitivity Index (ISI) | 0.145 units on a scale | Standard Deviation 0.697 |
| Placebo | Change From Baseline in the Insulin Sensitivity Index (ISI) | -0.112 units on a scale | Standard Deviation 0.669 |
Secondary
Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI)
QUICKI = 1/(log FPG + log FPI) where FPG = fasting plasma glucose (mg/dL); FPI = fasting plasma insulin (estimated based on fasting serum insulin; (μIU/mL)). Lower numbers reflect greater insulin resistance.
Time frame: Baseline to Day 29
Population: PD population includes all 81 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) | .0043 units on a scale | Standard Deviation 0.012 |
| KQ-791 Dose 2 | Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) | .003 units on a scale | Standard Deviation 0.013 |
| KQ-791 Dose 3 | Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) | .005 units on a scale | Standard Deviation 0.0125 |
| Placebo | Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI) | -.0012 units on a scale | Standard Deviation 0.0116 |
Secondary
Maximum Observed Plasma Concentration at Steady-state (Cmax_ss)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Cmax\_ss.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Maximum Observed Plasma Concentration at Steady-state (Cmax_ss) | 657.82 ng/mL | Standard Deviation 238.542 |
| KQ-791 Dose 2 | Maximum Observed Plasma Concentration at Steady-state (Cmax_ss) | 1164.65 ng/mL | Standard Deviation 568.489 |
| KQ-791 Dose 3 | Maximum Observed Plasma Concentration at Steady-state (Cmax_ss) | 7221.37 ng/mL | Standard Deviation 2672.18 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Maximum Observed Plasma Concentration (Cmax) | 747.56 ng/mL | Standard Deviation 163.768 |
| KQ-791 Dose 2 | Maximum Observed Plasma Concentration (Cmax) | 1484.74 ng/mL | Standard Deviation 341.712 |
| KQ-791 Dose 3 | Maximum Observed Plasma Concentration (Cmax) | 7204.70 ng/mL | Standard Deviation 2517.201 |
Secondary
Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Tmax\_ss.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss) | 5.10 hours | Standard Deviation 5 |
| KQ-791 Dose 2 | Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss) | 5.43 hours | Standard Deviation 5.69 |
| KQ-791 Dose 3 | Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss) | 3.83 hours | Standard Deviation 3.4 |
Secondary
Time of the Maximum Measured Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KQ-791 Dose 1 | Time of the Maximum Measured Plasma Concentration (Tmax) | 4.60 hours | Standard Deviation 3.251 |
| KQ-791 Dose 2 | Time of the Maximum Measured Plasma Concentration (Tmax) | 5.05 hours | Standard Deviation 3.395 |
| KQ-791 Dose 3 | Time of the Maximum Measured Plasma Concentration (Tmax) | 9.42 hours | Standard Deviation 8.663 |