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Trial record 2 of 3 for:    CBP-307

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

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ClinicalTrials.gov Identifier: NCT04818229
Recruitment Status : Not yet recruiting
First Posted : March 26, 2021
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
Suzhou Connect Biopharmaceuticals, Ltd.

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

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Drug: CBP-307 Drug: Placebo-matched CBP-307 Drug: Moxifloxacin (Avelox) Drug: Placebo-matched Moxifloxacin Phase 1

Detailed Description:
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled, single-site study to investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female subjects. The study is divided into a treatment period of 18 days and a follow-up period of 12 ± 2 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTc Interval in Healthy Subjects
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


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.

Drug: Placebo-matched Moxifloxacin
Placebo-matched Moxifloxacin tablets oral administration.

Placebo Comparator: Investigational Group 2
Moxifloxacin (positive control for method validation) and Placebo oral administration.
Drug: Placebo-matched CBP-307
Placebo-matched CBP-307 capsules oral administration.

Drug: Moxifloxacin (Avelox)
Moxifloxacin tablets oral administration。

Drug: Placebo-matched Moxifloxacin
Placebo-matched Moxifloxacin tablets oral administration.




Primary Outcome Measures :
  1. Change-from-baseline QT interval corrected for heart rate using Fridericia's method (QTcF) [ Time Frame: From Baseline to Day 16 ]
    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.


Secondary Outcome Measures :
  1. Change-from-baseline heart rate (HR) [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in heart rate (HR).

  2. Change-from-baseline PR [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in PR.

  3. Change-from-baseline QRS [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in QRS.

  4. Placebo-corrected change-from-baseline HR [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in HR with Placebo correction.

  5. Placebo-corrected change-from-baseline QTcF [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in QTcF with Placebo correction.

  6. Placebo-corrected change-from-baseline PR [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in PR with Placebo correction.

  7. Placebo-corrected change-from-baseline QRS [ Time Frame: From Baseline to Day 16 ]
    Change from Baseline in QRS with Placebo correction.

  8. Categorical outliers for QTcF [ Time Frame: From Baseline to Day 16 ]
    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.

  9. Categorical outliers for HR [ Time Frame: From Baseline to Day 16 ]
    For categorical outliers, decrease in HR from predose baseline >25% to an HR <50 bpm will be determined.

  10. Categorical outliers for PR [ Time Frame: From Baseline to Day 16 ]
    For categorical outliers, increase in PR from predose baseline >25% to a PR > 200 msec will be determined.

  11. Categorical outliers for QRS [ Time Frame: From Baseline to Day 16 ]
    For categorical outliers, increase in QRS from predose baseline >25% to a QRS >120 msec will be determined.

  12. Frequency of treatment-emergent changes of T-wave morphology [ Time Frame: From Baseline to Day 16 ]
    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.

  13. Frequency of treatment-emergent changes of U-wave presence [ Time Frame: From Baseline to Day 16 ]
    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.

  14. Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) [ Time Frame: From Baseline to Day 28 ± 2 ]
    Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) will be analyzed as a pharmacokinetic (PK) parameter.

  15. Area under the concentration-time curve from time zero to 24 hours postdose (AUC0-24) [ Time Frame: From Baseline to Day 28 ± 2 ]
    Area under the concentration-time curve from time zero to 24 hours postdose (AUC0-24) will be analyzed as a pharmacokinetic (PK) parameter.

  16. Maximum observed concentration (Cmax) [ Time Frame: From Baseline to Day 28 ± 2 ]
    Maximum observed concentration (Cmax) will be analyzed as a pharmacokinetic (PK) parameter.

  17. Time of the maximum observed concentration (tmax) [ Time Frame: From Baseline to Day 28 ± 2 ]
    Time of the maximum observed concentration (tmax) will be analyzed as a pharmacokinetic (PK) parameter.

  18. Incidence and severity of Adverse Event (AE) [ Time Frame: From Baseline to Day 28 ± 2 ]
    All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive methodology.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 60 bpm and 100 bpm inclusive);
    2. QTcF interval ≤450 msec for males and ≤470 msec for 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04818229


Contacts
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Contact: Max Meng +8651253577866 yhmeng@connectpharm.com
Contact: Amber Li +8651253577866 xwli@connectpharm.com

Locations
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Australia, South Australia
CMAX
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
Suzhou Connect Biopharmaceuticals, Ltd.
Investigators
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Study Director: Suzhou Connect Suzhou Connect Biopharmaceuticals, Ltd.
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Responsible Party: Suzhou Connect Biopharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT04818229    
Other Study ID Numbers: CBP-307AU002
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: March 26, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Autoimmune Diseases
Immune System Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs