A Double-Blind, Randomized, Placebo-Controlled Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of CT-868 in Healthy Overweight/Obese Participants and in Patients with Type 2 Diabetes Mellitus
Carmot Therapeutics
103 participants
Dec 19, 2018
Interventional
Conditions
Summary
This study is designed to assess the safety and tolerability, pharmacokinetics (how the drug is absorbed by the body) and pharmacodynamics (the effect the drug has on the body) of CT-868 when administered as single and multiple ascending doses in overweight/obese (otherwise healthy) participants and as multiple doses in patient with type 2 diabetes mellitus. The study will start with a low single dose and safety information will be reviewed by a safety review committee to confirm if higher doses can be given to sequential cohorts before giving multiple doses.
Eligibility
Inclusion Criteria20
- All study parts:
- Males and females aged 18-65 years (inclusive)
- Body mass index (BMI) 27-45 kg/m2
- No more than 5% weight loss within the preceding 3 months
- Normal blood pressure or well managed hypertension
- Females must be non-pregnant and non-lactating, and either surgically sterile
- Males must be surgically sterile, abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion,
- Part 1 only:
- Certified as healthy by comprehensive clinical assessment
- Part 1 and 2:
- Fasting plasma glucose less than or equal to 100 mg/dL (6.0 mmol/L)
- Part 2 and 3 only:
- Waist circumference greater than or equal to 102 cm (males) or greater than or equal to 88 cm (females)
- Part 3 only:
- Confirmed diagnosis of T2DM
- If not antidiabetic medication naïve, participants must be on a stable dose metformin or a DPP-4 inhibitor or a combination of these for at least 3 months prior to study enrollment
- Fasting insulin greater than 10 uIU/mL (> 60pmol/L)
- HbA1c equal to or greater than 7.0% and equal to but not greater than 10.0%
- Non-Alcoholic Fatty Liver Disease (NAFLD) as defined by an MRI-PDFF with greater to or equal to 10% steatosis
- Normal lipid profile or well managed dyslipidemia
Exclusion Criteria10
- Pregnant or lactating, or intending to become pregnant within 30 days after last dose of study drug
- Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater. Participants who have received an experimental therapy that has no half-life, like a vaccine, should have completed that therapy at least 12 weeks prior to randomization
- Any non-experimental vaccine within 12 weeks of randomization, until 4 weeks after the last dose, except for seasonal influenza vaccination which is permitted
- Use of any weight loss agent within 12 weeks prior to screening
- Surgery or hospitalization during the 4 weeks prior to screening
- Within the last 2 years, unstable or clinically significant cardiovascular disease
- Part 3 only:
- Use of glitazones, sulfonylureas, or injectables (glucagon-like peptide 1 [GLP-1] mimetics, insulin) in the 3 months prior to study enrollment
- Persistent hyperglycemia, defined as a glucose level >270 mg/dL, not controlled by a stable dose of an a-glucosidase inhibitor or metformin or a DPP-4 inhibitor or a combination of these and/or diet/exercise
- A diagnosis of clinically significant diabetic neuropathy, retinopathy, nephropathy or renal impairment
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Interventions
Single ascending dose cohorts (Part 1): Completed Administered doses of CT-868 or matched placebo: 0.1mg, 0.5mg, 1.5mg, 3.0mg, 5.0mg, 7.5mg and 11.0mg given by subcutaneous (SC) injection. Injection administered by staff in the study unit. Multiple ascending dose cohorts (Part 2): Completed Administered doses of CT-868 or matched placebo: 0.75mg, 1.5mg and 5mg given by SC injection once daily for 14 days. Injections administered by staff in the study unit. Multiple dose in Type 2 diabetes (T2DM) (Part 3): Open to enrollment Following instructions provided by the clinical site staff, participants will self-administer once daily SC injection(s) of CT-868 or matched placebo for 28 days. Dosing will commence at 1.0mg for seven days, and if the dose level is tolerated, be increased to 1.5mg for a further seven days and then be increased again, subject to tolerance, to 2.25mg for a further fourteen days. The total duration of study participation is 13 weeks comprising of the screening period, two inpatient stays in the clinical unit: initially for 6 nights and then for a further 3 nights, three outpatient visits and two follow-up visits. Participants may only take part in one cohort for the study
Locations(3)
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ACTRN12618001988246