First in Human Study of CT-1500 in Healthy Participants

First in Human Study in Healthy Subjects to Investigate the Safety, Tolerability and Pharmacokinetics of Single Ascending and Repeat Doses of CT-1500

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CT-1500; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs) and Serious Adverse Events (SAEs) during the SAD part of the study	Incidence and severity of AEs and SAEs	Initiation of dosing through 7 days post dose
Adverse Events and Serious Adverse Events during the MAD part of the study	Incidence and severity of AEs and SAEs	Initiation of dosing through 14 days post dose
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)	Change in QT interval from baseline	Initiation of dosing through 7 days post dose
Tolerability of CT-1500 as defined by change from baseline in Electrocardiogram assessment (MAD)	Change in QT interval from baseline	Initiation of dosing through 14 days post dose
Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (SAD)	Change from baseline in Forced Expiratory Volume in 1 second (FEV1)	Initiation of dosing through 7 days post dose
Tolerability of CT-1500 as defined by change from baseline in Spirometry assessment (MAD)	Change from baseline in Forced Expiratory Volume in 1 second (FEV1)	Initiation of dosing through 14 days post dose
Change in Renal function from baseline (SAD)	Renal Function as assessed by change in estimated Glomerular Filtration Rate from baseline	Initiation of dosing through 24 hours post dose
Change in Renal function from baseline (MAD)	Renal Function as assessed by change in estimated Glomerular Filtration Rate from baseline	Initiation of dosing on Day 1 through 24 hours and initiation of dosing on Day 7 through 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter: AUC-last (SAD)	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	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: AUC-last (SAD)	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	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: AUC-last (SAD)	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	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: AUC-last (MAD)	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	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: AUC-last (MAD)	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	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: AUC-last (MAD)	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	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: AUC-inf (SAD)	Area under the plasma concentration time curve from time zero to infinity of CT-1500 is observed during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: AUC-inf (MAD)	Area under the plasma concentration time curve from time zero to infinity of CT-1500 is observed during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Cmax (SAD)	Maximal measured plasma concentration (Cmax) of CT-1500 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Cmax (SAD)	Maximal measured plasma concentration of metabolite CT-1517 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Cmax (SAD)	Maximal measured plasma concentration of metabolite CT-1518 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Cmax (MAD)	Maximal measured plasma concentration of CT-1500 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Cmax (MAD)	Maximal measured plasma concentration of metabolite CT-1517 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Cmax (MAD)	Maximal measured plasma concentration of metabolite CT-1518 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Tmax (SAD)	Time when Maximal measured plasma concentration is observed (Tmax) of CT-1500 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Tmax (SAD)	Time when Maximal measured plasma concentration is observed of metabolite CT-1517 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Tmax (SAD)	Time when Maximal measured plasma concentration is observed of metabolite CT-1518 during the SAD part of the study	Baseline (predose) through 48 hours post dose
Pharmacokinetic parameter: Tmax (MAD)	Time when Maximal measured plasma concentration is observed of CT-1500 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Tmax (MAD)	Time when Maximal measured plasma concentration is observed of metabolite CT-1517 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours
Pharmacokinetic parameter: Tmax (MAD)	Time when Maximal measured plasma concentration is observed of metabolite CT-1518 during the MAD part of the study	Baseline (predose) on Day 1 through 24 hours post dose and Baseline (predose) on Day 7 through 24 hours

Collaborators and Investigators

• Sponsor: Circadian Therapeutics Ltd
• Collaborators: Neuroscience Trials Australia
• Investigators: Principal Investigator: Philip Ryan, Dr, Nucleus Network

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Actual): July 7, 2022
• Study Completion (Actual): July 7, 2022

Study Registration Dates

• First Submitted: September 13, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CT-1500-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Sponsor will consider requests from appropriately qualified researchers for study information and participant data upon a formal request to contact@circadiantherapeutics.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No