A Study to Investigate the Effects of CBP-307 on the Heart Rate-corrected QT Interval (QTc) in Healthy Subjects

A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTc Interval in Healthy Subjects

This study will investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: CBP-307; Drug: Placebo-matched CBP-307; Drug: Moxifloxacin (Avelox); Drug: Placebo-matched Moxifloxacin

Detailed Description

This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female subjects.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX
• United States
  • Florida
    • Hialeah, Florida, United States, 33014
      • Clinical Pharmacology of Miami (CPMI), LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females, of any race, between 18 and 60 years of age, inclusive.
2. Body mass index between 18.0 and 30.0 kg/mE2, inclusive.
3. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and confirmed at check-in as assessed by the investigator (or designee).
4. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception. Negative pregnancy test for females of childbearing potential at screening (blood test) and check-in (urine test).
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure between 90 and 140 mmHg (inclusive) at screening on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest.

6. No clinically significant history or presence of ECG findings as judged by the investigator at screening and check-in, including each criterion as listed below:

   1. Normal sinus rhythm (HR between 55 bpm and 100 bpm inclusive);
   2. QTcF interval ≤450 msec for males and females;
   3. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec;
   4. PR interval ≤200 msec.
7. Has serum potassium, calcium, and magnesium levels within the normal reference range at screening, as judged by the investigator.
8. Able to swallow multiple tablets (based on subject's verbal confirmation).
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

-

Subjects will be excluded from the study if they satisfy any of the following criteria at the screening visit unless otherwise stated:

1. Subject is mentally or legally incapacitated or has had significant history of recent mental health issues requiring medication and/or hospitalization at the time of the screening visit or expected during the conduct of the study.
2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee). Note: Childhood asthma that is considered recovered or seasonal allergies that are not currently active or requiring treatment are allowed.
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, or inactive ingredients.
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs.
6. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs within 6 months prior to the first dose of study drug (uncomplicated appendectomy and hernia repair will be allowed).

7. History or presence of:

   1. Hypokalemia, in the opinion of the investigator (or designee);
   2. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or family history of Long QT Syndrome);
   3. Sick sinus syndrome, second, or third degree atrioventricular block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities;
   4. Repeated or frequent syncope or vasovagal episodes;
   5. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory disorders.

8. Clinically significant abnormalities (as judged by the investigator in laboratory tests results [out-of-range results confirmed on repeat]), including but not limited to the following parameters:

   1. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin greater than 1.5 × upper limit of normal;
   2. hemoglobin <10 g/dL, WBC <3.0 ×10E9/L, neutrophils <1.5 ×10E9/L, lymphocytes <0.8 ×10E9/L and platelets <100 ×10E9/L or >1200 × 10E9/L;
9. History or evidence of alcoholism or drug/chemical abuse within 2 years prior to check-in.
10. Alcohol consumption of >10 units per week for males and females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in.
12. Positive hepatitis panel, positive syphilis test, and/or positive human immunodeficiency virus test.
13. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 28 days prior to the first dose of study treatment on Day 1. The 28-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
14. Participation in a previous clinical study where subjects received CBP-307.
15. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 28 days prior to first dose of study treatment on Day 1.
16. Use or intend to use any prescription medications/products within 14 days prior to first dose of study drug (Day 1) and throughout the study, unless deemed acceptable by the investigator (or designee). Note: For females only, the use hormonal contraception, hormone replacement therapy or oral, implantable, transdermal, injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is not acceptable, except for Mirena®.
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP enzymes and/or P-gp, including St. John's Wort, for days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the investigator or designee to confirm the lack of PK/PD interaction with the study drug.
18. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
19. Use or intend to use any nonprescription medications/products including antacids, vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or positive cotinine at screening or check-in.
21. Has been on a diet incompatible with the on-study diet (including an extreme diet which resulted in a significant weight change for whatever reason), in the opinion of the investigator, within the 28 days prior to the first dose of study treatment, and throughout the study.
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours prior to check-in until discharge.
23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to check-in.
24. Receipt of blood products within 2 months prior to check-in.
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
26. Poor peripheral venous access.
27. Subjects who, in the opinion of the investigator (or designee), should not participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Group 1; Therapeutic and supratherapeutic multiple oral doses of CBP-307.	Drug: CBP-307; CBP-307 capsules oral administration.; Drug: Placebo-matched CBP-307; Placebo-matched CBP-307 capsules oral administration.
Placebo Comparator: Investigational Group 2A; Moxifloxacin (positive control for method validation) and Placebo oral administration.	Drug: Moxifloxacin (Avelox); Moxifloxacin tablets oral administration。; Drug: Placebo-matched Moxifloxacin; Placebo-matched Moxifloxacin tablets oral administration.
Placebo Comparator: Investigational Group 2B; Moxifloxacin (positive control for method validation) and Placebo oral administration.	Drug: Moxifloxacin (Avelox); Moxifloxacin tablets oral administration。; Drug: Placebo-matched Moxifloxacin; Placebo-matched Moxifloxacin tablets oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change-from-baseline QT Interval Corrected for Heart Rate Using Fridericia's Method (QTcF)	Change from Baseline in QT interval corrected for heart rate using Fridericia's method (QTcF) to evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma concentrations.	From Baseline to Day 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change-from-baseline Heart Rate (HR)	Change from Baseline in heart rate (HR).	From Baseline at Day 16
Change-from-baseline PR	Change from Baseline in PR.	From Baseline at Day 16
Change-from-baseline QRS	Change from Baseline in QRS.	From Baseline at Day 16
Placebo-corrected Change-from-baseline HR	Placebo-corrected Change-from-baseline HR based on Change-from-baseline Heart Rate (HR) reported in Outcome Measure 2	From Baseline to Day 16
Placebo-corrected Change-from-baseline QTcF	Placebo-corrected change-from-baseline QT Interval Corrected for Heart Rate Using Fridericia's Method (QTcF) based on Change-from-baseline QTcF reported in Outcome Measure 1	From Baseline to Day 16
Placebo-corrected Change-from-baseline PR	Placebo-corrected change-from-baseline PR based on Change-from-baseline PR reported in Outcome Measure 3	From Baseline to Day 16
Placebo-corrected Change-from-baseline QRS	Placebo-corrected change-from-baseline QRS based on Change-from-baseline QRS reported in Outcome Measure 4	From Baseline to Day 16
Categorical Outliers for QTcF	For categorical outliers, the number (percentage) of subjects as well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or >60 msec.	From Baseline to Day 16
Categorical Outliers for HR	For categorical outliers, decrease in HR from predose baseline >25% to an HR <50 bpm will be determined.	From Baseline to Day 16
Categorical Outliers for PR	For categorical outliers, increase in PR from predose baseline >25% to a PR > 200 msec will be determined.	From Baseline to Day 16
Categorical Outliers for QRS	For categorical outliers, increase in QRS from predose baseline >25% to a QRS >120 msec will be determined.	From Baseline to Day 16
Frequency of Treatment-emergent Changes of T-wave Morphology	For T-wave morphology, the analyses will be focused on change from baseline with counts (percentages) for both the number of subjects and the number of timepoints.	From Baseline to Day 16
Frequency of Treatment-emergent Changes of U-wave Presence	For U-wave presence, the analyses will be focused on change from baseline with counts (percentages) for both the number of subjects and the number of timepoints.	From Baseline to Day 16
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)	Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) will be analyzed as a pharmacokinetic (PK) parameter.	From Baseline to Day 29 ± 2
Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24)	Area under the concentration-time curve from time zero to 24 hours postdose (AUC0-24) will be analyzed as a pharmacokinetic (PK) parameter.	From Baseline to Day 29 ± 2
Maximum Observed Concentration (Cmax)	Maximum observed concentration (Cmax) will be analyzed as a pharmacokinetic (PK) parameter.	From Baseline to Day 29 ± 2
Time of the Maximum Observed Concentration (Tmax)	Time of the maximum observed concentration (tmax) will be analyzed as a pharmacokinetic (PK) parameter.	From Baseline to Day 29 ± 2
Incidence and Severity of Adverse Event (AE)	All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive methodology. 14.3.1.1 TEAE	From Baseline to Day 29 ± 2

Collaborators and Investigators

• Sponsor: Connect Biopharma Australia Pty Ltd
• Investigators: Study Director: Australia Connect, Connect Biopharma Australia Pty Ltd; Study Director: Suzhou Connect, Suzhou Connect Biopharmaceuticals, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): March 20, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Contraceptive Agents, Hormonal; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Reproductive Control Agents; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
• Other Study ID Numbers: CBP-307AU002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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