Clinical trial NCT05070702: First in Human Study of CT-1500 in Healthy Participants
Official title: First in Human Study in Healthy Subjects to Investigate the Safety, Tolerability and Pharmacokinetics of Single Ascending and Repeat Doses of CT-1500
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Circadian Therapeutics Ltd
Sponsor class: INDUSTRY
Collaborators: name: Neuroscience Trials Australia
First posted: 2021-10-07
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Ascending Single Doses followed by Ascending Multiple Doses of Study Intervention
Primary purpose: OTHER

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.

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.

Eligibility 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

Primary outcomes:
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs) during the SAD part of the study
timeFrame: Initiation of dosing through 7 days post dose
measure: Adverse Events and Serious Adverse Events during the MAD part of the study
timeFrame: Initiation of dosing through 14 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Heart Rate (SAD)
timeFrame: Initiation of dosing through 7 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Heart Rate (MAD)
timeFrame: Initiation of dosing through 14 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Respiratory Rate (SAD)
timeFrame: Initiation of dosing through 7 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Respiratory Rate (MAD)
timeFrame: Initiation of dosing through 14 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Electrocardiogram Assessment (SAD)
timeFrame: Initiation of dosing through 7 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Electrocardiogram assessment (MAD)
timeFrame: Initiation of dosing through 14 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (SAD)
timeFrame: Initiation of dosing through 7 days post dose
measure: Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (MAD)
timeFrame: Initiation of dosing through 14 days post dose
measure: Change in Renal function from baseline (SAD)
timeFrame: Initiation of dosing through 24 hours post dose
measure: Change in Renal function from baseline (MAD)
timeFrame: Initiation of dosing on Day 1 through 24 hours and initiation of dosing on Day 7 through 24 hours
Secondary outcomes:
measure: Pharmacokinetic parameter: AUC-last (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: AUC-last (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: AUC-last (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: AUC-last (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: AUC-last (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: AUC-last (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: AUC-inf (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: AUC-inf (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Cmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Cmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Cmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Cmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Cmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Cmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Tmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Tmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Tmax (SAD)
timeFrame: Baseline (predose) through 48 hours post dose
measure: Pharmacokinetic parameter: Tmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Tmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
measure: Pharmacokinetic parameter: Tmax (MAD)
timeFrame: Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
affiliation: Nucleus Network
name: Philip Ryan, Dr
role: PRINCIPAL_INVESTIGATOR
References: