Diabetes Mellitus, Type 2Phase 1NCT02445911
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus
A Phase 1 study testing KQ-791 in people with Diabetes Mellitus, Type 2, run by Kaneq Bioscience Limited at 4 sites in United States.
Trial summary
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- KQ-791
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2015to Feb 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Celerion
Lincoln, Nebraska, 68502
Clinical Pharmacology of Miami, Inc.
Miami, Florida, 33014
Orlando Clinical Research Center
Orlando, Florida, 32809
Celerion
Tempe, Arizona, 85283
About this study
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of KQ-791 in Subjects With Type 2 Diabetes
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- KQ-791, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KQ-791Drug
Capsules administered orally
PlaceboDrug
Capsules administered orally
| Study group | Role | What they receive |
|---|---|---|
| KQ-791 Dose 1 | Experimental | Single loading dose on day 1, followed by single doses on days 8, 15, 22, 29 Receives: Drug: KQ-791 |
| KQ-791 Dose 2 | Experimental | Single loading dose on day 1, followed by a daily dose for 28 days Receives: Drug: KQ-791 |
| KQ-791 Dose 3 | Experimental | Single loading dose on day 1 or days 1-2, followed by a daily dose for 28 days Receives: Drug: KQ-791 |
| Placebo | Placebo comparator | Multiple ascending doses matching KQ-791 dose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Day 29
Number of Participants With One or More Treatment-Emergent Adverse Events
Measured: Baseline to Day 29
Secondary outcomes (16)
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.
Measured: Baseline to Day 29
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.
Measured: Baseline to Day 29
Change From Baseline in Beta Cell Function
Evaluated as beta index = (Insulin Area Under the Effect Curve (AUEC) in MMTT/Glucose AUEC in MMTT)
Measured: Baseline to Day 29
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.
Measured: Baseline to Day 29
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
Measured: Baseline to Day 29
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.
Measured: Baseline to Day 29
Change From Baseline in Postprandial Glucose
Measured: Baseline to Day 29
Change From Baseline in HbA1c
Measured: Baseline to Day 29
Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24)
Measured: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
Measured: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Time of the Maximum Measured Plasma Concentration (Tmax)
Measured: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve (AUCtau)
Measured: 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
Maximum Observed Plasma Concentration at Steady-state (Cmax_ss)
Measured: 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
Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss)
Measured: 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
Apparent Terminal Elimination Half-life (t1/2)
Measured: 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
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)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study startJun 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaneq Bioscience Limited
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Email: daniel.bouthillier@Kaneq.ca, Study director, Kaneq Bioscience
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445911
- Sponsor's protocol ID
- KQ-791-02
- Status last verified
- Nov 2019
- First submitted
- 13 May 2015
- Last updated
- 26 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of KQ-791 in Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02445911
- Acronym / sponsor ID
- KQ-791-02
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Kaneq Bioscience LimitedUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 15 May 2015 (estimated)
- Results
- Posted 30 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| KQ-791 Dose 1 | Experimental | Drug: KQ-791Single loading dose on day 1, followed by single doses on days 8, 15, 22, 29 |
| KQ-791 Dose 2 | Experimental | Drug: KQ-791Single loading dose on day 1, followed by a daily dose for 28 days |
| KQ-791 Dose 3 | Experimental | Drug: KQ-791Single loading dose on day 1 or days 1-2, followed by a daily dose for 28 days |
| Placebo | Placebo comparator | Drug: PlaceboMultiple ascending doses matching KQ-791 dose |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KQ-791Capsules administered orally | Drug | KQ-791 Dose 1, KQ-791 Dose 2, KQ-791 Dose 3 |
| PlaceboCapsules administered orally | Drug | Placebo |
Primary outcome
Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo
Time frame: 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
Time frame: Baseline to Day 29
16 secondary outcomes
Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI)
Time frame: Baseline to Day 29
Change From Baseline in the Insulin Sensitivity Index (ISI)
Time frame: Baseline to Day 29
Change From Baseline in Beta Cell Function
Time frame: Baseline to Day 29
Change From Baseline in Disposition Index
Time frame: Baseline to Day 29
Change From Baseline in the Hepatic Insulin Resistance Index
Time frame: Baseline to Day 29
Change From Baseline in 7-point Average Blood Glucose
Time frame: Baseline to Day 29
Change From Baseline in Postprandial Glucose
Time frame: Baseline to Day 29
Change From Baseline in HbA1c
Time frame: Baseline to Day 29
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
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
Time of the Maximum Measured Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose
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
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
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
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
Accumulation Index (AI)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Email: daniel.bouthillier@Kaneq.ca study director
Kaneq Bioscience
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KQ-791 in people with Diabetes Mellitus, Type 2, run by Kaneq Bioscience Limited at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo (time frame: Baseline to Day 29). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2019.