First in Human Study of CT-1500 in Healthy Participants
Study Details
Study Description
Brief Summary
This study is a single center, randomized, placebo-controlled, double-blind study of CT-1500 in healthy volunteers. The study will evaluate the safety, tolerability and pharmacokinetics of single ascending doses and multiple ascending doses of orally administered CT-1500 compared to placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is a single center, randomized, placebo-controlled, double-blind study of CT-1500 in healthy volunteers. The study will evaluate the safety, tolerability and pharmacokinetics of single ascending doses and multiple ascending doses of orally administered CT-1500 compared to placebo. It is planned for 5 dose levels to be investigated in the single ascending dose (SAD) part (Part 1) of the study, between 5 mg to 120 mg. Three dose levels are proposed for investigation in the multiple ascending dose (MAD) part (Part 2) of the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CT-1500 Active (SAD) 6 out of 8 participants per cohort (up to 5 cohorts) will be randomized to receive a single oral dose of CT-1500 between 5 mg and 120 mg |
Drug: CT-1500
Hard Capsule
|
| Placebo Comparator: Placebo (SAD) 2 out of 8 participants per cohort (up to 5 cohorts) will be randomized to receive a single oral dose of matching placebo |
Drug: Placebo
Hard Capsule
|
| Experimental: CT-1500 Active (MAD) 6 out of 8 participants per cohort (up to 3 cohorts) will be randomized to receive 7 daily oral doses of CT-1500 between 5 and 45 mg |
Drug: CT-1500
Hard Capsule
|
| Placebo Comparator: Placebo (MAD) 2 out of 8 participants per cohort (up to 3 cohorts) will be randomized to receive 7 daily oral doses of matching placebo |
Drug: Placebo
Hard Capsule
|
Outcome Measures
Primary Outcome Measures
- Adverse Events (AEs) and Serious Adverse Events (SAEs) during the SAD part of the study [Initiation of dosing through 7 days post dose]
Incidence and severity of AEs and SAEs
- Adverse Events and Serious Adverse Events during the MAD part of the study [Initiation of dosing through 14 days post dose]
Incidence and severity of AEs and SAEs
- Tolerability of CT-1500 as defined by change from baseline in Heart Rate (SAD) [Initiation of dosing through 7 days post dose]
- Tolerability of CT-1500 as defined by change from baseline in Heart Rate (MAD) [Initiation of dosing through 14 days post dose]
- Tolerability of CT-1500 as defined by change from baseline in Respiratory Rate (SAD) [Initiation of dosing through 7 days post dose]
- Tolerability of CT-1500 as defined by change from baseline in Respiratory Rate (MAD) [Initiation of dosing through 14 days post dose]
- Tolerability of CT-1500 as defined by change from baseline in Electrocardiogram Assessment (SAD) [Initiation of dosing through 7 days post dose]
Change in QT interval from baseline
- Tolerability of CT-1500 as defined by change from baseline in Electrocardiogram assessment (MAD) [Initiation of dosing through 14 days post dose]
Change in QT interval from baseline
- Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (SAD) [Initiation of dosing through 7 days post dose]
Change from baseline in Forced Expiratory Volume in 1 second (FEV1)
- Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (MAD) [Initiation of dosing through 14 days post dose]
Change from baseline in Forced Expiratory Volume in 1 second (FEV1)
- Change in Renal function from baseline (SAD) [Initiation of dosing through 24 hours post dose]
Renal Function as assessed by change in estimated Glomerular Filtration Rate from baseline
- Change in Renal function from baseline (MAD) [Initiation of dosing on Day 1 through 24 hours and initiation of dosing on Day 7 through 24 hours]
Renal Function as assessed by change in estimated Glomerular Filtration Rate from baseline
Secondary Outcome Measures
- Pharmacokinetic parameter: AUC-last (SAD) [Baseline (predose) through 48 hours post dose]
Area under the plasma concentration time curve (AUC) from time zero until the last measurable concentration of CT-1500 is observed during the SAD part of the study
- Pharmacokinetic parameter: AUC-last (SAD) [Baseline (predose) through 48 hours post dose]
Area under the plasma concentration time curve from time zero until the last measurable concentration of metabolite CT-1517 is observed during the SAD part of the study
- Pharmacokinetic parameter: AUC-last (SAD) [Baseline (predose) through 48 hours post dose]
Area under the plasma concentration time curve from time zero until the last measurable concentration of metabolite CT-1518 is observed during the SAD part of the study
- Pharmacokinetic parameter: AUC-last (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Area under the plasma concentration time curve from time zero until the last measurable concentration of CT-1500 is observed during the MAD part of the study
- Pharmacokinetic parameter: AUC-last (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Area under the plasma concentration time curve from time zero until the last measurable concentration of metabolite CT-1517 is observed during the MAD part of the study
- Pharmacokinetic parameter: AUC-last (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Area under the plasma concentration time curve from time zero until the last measurable concentration of metabolite CT-1518 is observed during the MAD part of the study
- Pharmacokinetic parameter: AUC-inf (SAD) [Baseline (predose) through 48 hours post dose]
Area under the plasma concentration time curve from time zero to infinity of CT-1500 is observed during the SAD part of the study
- Pharmacokinetic parameter: AUC-inf (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Area under the plasma concentration time curve from time zero to infinity of CT-1500 is observed during the MAD part of the study
- Pharmacokinetic parameter: Cmax (SAD) [Baseline (predose) through 48 hours post dose]
Maximal measured plasma concentration (Cmax) of CT-1500 during the SAD part of the study
- Pharmacokinetic parameter: Cmax (SAD) [Baseline (predose) through 48 hours post dose]
Maximal measured plasma concentration of metabolite CT-1517 during the SAD part of the study
- Pharmacokinetic parameter: Cmax (SAD) [Baseline (predose) through 48 hours post dose]
Maximal measured plasma concentration of metabolite CT-1518 during the SAD part of the study
- Pharmacokinetic parameter: Cmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Maximal measured plasma concentration of CT-1500 during the MAD part of the study
- Pharmacokinetic parameter: Cmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Maximal measured plasma concentration of metabolite CT-1517 during the MAD part of the study
- Pharmacokinetic parameter: Cmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Maximal measured plasma concentration of metabolite CT-1518 during the MAD part of the study
- Pharmacokinetic parameter: Tmax (SAD) [Baseline (predose) through 48 hours post dose]
Time when Maximal measured plasma concentration is observed (Tmax) of CT-1500 during the SAD part of the study
- Pharmacokinetic parameter: Tmax (SAD) [Baseline (predose) through 48 hours post dose]
Time when Maximal measured plasma concentration is observed of metabolite CT-1517 during the SAD part of the study
- Pharmacokinetic parameter: Tmax (SAD) [Baseline (predose) through 48 hours post dose]
Time when Maximal measured plasma concentration is observed of metabolite CT-1518 during the SAD part of the study
- Pharmacokinetic parameter: Tmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Time when Maximal measured plasma concentration is observed of CT-1500 during the MAD part of the study
- Pharmacokinetic parameter: Tmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Time when Maximal measured plasma concentration is observed of metabolite CT-1517 during the MAD part of the study
- Pharmacokinetic parameter: Tmax (MAD) [Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours]
Time when Maximal measured plasma concentration is observed of metabolite CT-1518 during the MAD part of the study
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Generally healthy with the exception of those medical conditions allowed per the study criteria
-
Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures
-
Body Mass Index (BMI) of 18.5 to 32 kg/m2 and weight >48 kg
-
Systolic Blood Pressure (BP) of 90-140 mmHg, Diastolic BP of 40-90 mmHg and Heart Rate between 40 and 100 bpm
-
Forced Expiratory Volume in one second (FEV1) > 85% predicted
-
Clinical laboratory results at screening and Day -1 to be within normal limits unless deemed as not clinically significant by the investigator
-
Willing to consume bovine containing products (investigational product capsules are bovine gelatin in origin);
-
Agree not to donate blood or plasma products for at least 30 days after the end of study (EOS) visit
-
Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1, must not be breastfeeding, lactating or planning a pregnancy and must use an acceptable form of contraception during the treatment period and for 32 days after the last dose
-
Male participants with a female partner of childbearing potential must agree to use an acceptable form of contraception during the treatment period and for 92 days after the last dose
Exclusion Criteria:
-
Significant current or historical disease, including intercurrent illness in the 4 weeks prior to screening
-
Current or historical diagnosis of sleep disorders
-
Hepatic disorders other than benign unconjugated hyperbilirubinaemia
-
History of moderate or severe psychiatric illness
-
History of severe allergy or anaphylaxis to any drug, food, toxin or other exposure
-
Heavy caffeine drinker in the last 3 months. If subjects are willing to reduce their caffeine intake for 14 days prior to first dose and for the duration of the study, they can participate
-
Hypersensitivity to CT-1500 or any of the inert excipients in the capsule formulation
-
Positive hepatitis B surface antigen (HBsAg), positive hepatitis C antibody (HCV) or positive human immunodeficiency virus (HIV) test
-
Treatment with an investigational drug within 30 days or less than 5 half-lives (whichever is longer) prior to screening
-
Use of prescription medication within 14 days prior to investigational product administration until the end of study visit, with the exception of oral contraceptives.
-
Use of over-the-counter medication and supplements for 7 days prior to investigation product administration until the end of study visit. Exceptions at the discretion of the investigator.
-
Receipt of a Coronavirus disease 2019 (COVID-19) vaccine within 14 days prior to investigational product administration or a planned second dose of a COVID-19 vaccine during study participation
-
Use of tobacco or nicotine-containing products in excess of 2 cigarettes per day within 1 month prior to screening
-
Major surgery in the 6 months preceeding screening or planned surgery during the study
-
Donated blood or blood products or had a substantial loss of blood with 3 months prior to screening
-
A history of drug abuse or addiction
-
A history of alcoholism or consumption of more than 3 alcoholic drinks per day or consumption of alcohol within 48 hours prior to first dose
-
Unable to abstain from grapefruit-containing foods or beverages or Seville orange-containing foods or beverages from 48 hours prior to investigational product administration until completion of the confinement period;
-
Unable to avoid heavy exercise (eg, marathon runners, weight-lifters) from 48 hours prior to investigational product administration until completion of the confinement period
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nucleus Network | Melbourne | Victoria | Australia | 3004 |
Sponsors and Collaborators
- Circadian Therapeutics Ltd
- Neuroscience Trials Australia
Investigators
- Principal Investigator: Philip Ryan, Dr, Nucleus Network
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT-1500-01