Autoimmune Diseases
Conditions
Brief summary
This study will investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy subjects.
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.
Interventions
DRUGCBP-307
CBP-307 capsules oral administration.
DRUGPlacebo-matched CBP-307
Placebo-matched CBP-307 capsules oral administration.
Moxifloxacin tablets oral administration。
DRUGPlacebo-matched Moxifloxacin
Placebo-matched Moxifloxacin tablets oral administration.
Sponsors
Connect Biopharma Australia Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change-from-baseline QT Interval Corrected for Heart Rate Using Fridericia's Method (QTcF) | 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
| Measure | Time frame | Description |
|---|---|---|
| Change-from-baseline PR | From Baseline at Day 16 | Change from Baseline in PR. |
| Change-from-baseline QRS | From Baseline at Day 16 | Change from Baseline in QRS. |
| Placebo-corrected Change-from-baseline HR | From Baseline to Day 16 | Placebo-corrected Change-from-baseline HR based on Change-from-baseline Heart Rate (HR) reported in Outcome Measure 2 |
| Placebo-corrected Change-from-baseline QTcF | From Baseline to Day 16 | 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 |
| Placebo-corrected Change-from-baseline PR | From Baseline to Day 16 | Placebo-corrected change-from-baseline PR based on Change-from-baseline PR reported in Outcome Measure 3 |
| Placebo-corrected Change-from-baseline QRS | From Baseline to Day 16 | Placebo-corrected change-from-baseline QRS based on Change-from-baseline QRS reported in Outcome Measure 4 |
| Categorical Outliers for QTcF | 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. |
| Categorical Outliers for HR | From Baseline to Day 16 | For categorical outliers, decrease in HR from predose baseline \>25% to an HR \<50 bpm will be determined. |
| Change-from-baseline Heart Rate (HR) | From Baseline at Day 16 | Change from Baseline in heart rate (HR). |
| Categorical Outliers for QRS | From Baseline to Day 16 | For categorical outliers, increase in QRS from predose baseline \>25% to a QRS \>120 msec will be determined. |
| Frequency of Treatment-emergent Changes of T-wave Morphology | 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. |
| Frequency of Treatment-emergent Changes of U-wave Presence | 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. |
| Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) | From Baseline to Day 29 ± 2 | Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) will be analyzed as a pharmacokinetic (PK) parameter. |
| Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) | From Baseline to Day 29 ± 2 | Area under the concentration-time curve from time zero to 24 hours postdose (AUC0-24) will be analyzed as a pharmacokinetic (PK) parameter. |
| Maximum Observed Concentration (Cmax) | From Baseline to Day 29 ± 2 | Maximum observed concentration (Cmax) will be analyzed as a pharmacokinetic (PK) parameter. |
| Time of the Maximum Observed Concentration (Tmax) | From Baseline to Day 29 ± 2 | Time of the maximum observed concentration (tmax) will be analyzed as a pharmacokinetic (PK) parameter. |
| Incidence and Severity of Adverse Event (AE) | From Baseline to Day 29 ± 2 | All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive methodology. 14.3.1.1 TEAE |
| Categorical Outliers for PR | From Baseline to Day 16 | For categorical outliers, increase in PR from predose baseline \>25% to a PR \> 200 msec will be determined. |
Countries
Australia, United States
Participant flow
Pre-assignment details
Placebo was administered to all subjects on Day -1, and assigned study treatments were administered on Days 1 through 16.
Participants by arm
| Arm | Count |
|---|---|
| Investigational Group 1 Therapeutic and supratherapeutic multiple oral doses of CBP-307.
CBP-307: CBP-307 capsules oral administration.
Placebo-matched CBP-307: Placebo-matched CBP-307 capsules oral administration. | 55 |
| Investigational Group 2A Moxifloxacin (positive control for method validation) and Placebo oral administration.
Moxifloxacin (Avelox): Moxifloxacin tablets oral administration。
Placebo-matched Moxifloxacin: Placebo-matched Moxifloxacin tablets oral administration. | 28 |
| Investigational Group 2B Moxifloxacin (positive control for method validation) and Placebo oral administration.
Moxifloxacin (Avelox): Moxifloxacin tablets oral administration。
Placebo-matched Moxifloxacin: Placebo-matched Moxifloxacin tablets oral administration. | 29 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | The cohort was canceled due to COVID-19 | 20 | 10 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Investigational Group 1 | Investigational Group 2A | Investigational Group 2B | Total |
|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 11.17 | 41.6 years STANDARD_DEVIATION 11.25 | 41.1 years STANDARD_DEVIATION 11.1 | 41.6 years STANDARD_DEVIATION 11.07 |
| Body Mass Index | 26.74 kg/m^2 STANDARD_DEVIATION 2.656 | 26.95 kg/m^2 STANDARD_DEVIATION 2.423 | 27.01 kg/m^2 STANDARD_DEVIATION 2.866 | 26.87 kg/m^2 STANDARD_DEVIATION 2.636 |
| Body Weight | 76.80 Kg STANDARD_DEVIATION 12.481 | 76.70 Kg STANDARD_DEVIATION 10.636 | 76.39 Kg STANDARD_DEVIATION 10.89 | 76.67 Kg STANDARD_DEVIATION 11.543 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 22 Participants | 23 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 6 Participants | 6 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.13 cm STANDARD_DEVIATION 10.712 | 168.45 cm STANDARD_DEVIATION 8.96 | 168.14 cm STANDARD_DEVIATION 9.821 | 168.71 cm STANDARD_DEVIATION 9.994 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 4 Participants | 2 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 45 Participants | 23 Participants | 25 Participants | 93 Participants |
| Sex: Female, Male Female | 23 Participants | 13 Participants | 11 Participants | 47 Participants |
| Sex: Female, Male Male | 32 Participants | 15 Participants | 18 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 | 0 / 55 | 0 / 50 | 0 / 55 | 0 / 57 |
| other Total, other adverse events | 4 / 55 | 7 / 55 | 14 / 55 | 12 / 50 | 22 / 55 | 22 / 57 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 | 0 / 55 | 0 / 50 | 0 / 55 | 0 / 57 |
Outcome results
Primary
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.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Change-from-baseline QT Interval Corrected for Heart Rate Using Fridericia's Method (QTcF) | 1.5 msec | Standard Error 2.46 |
| Investigational Group 2A+2B | Change-from-baseline QT Interval Corrected for Heart Rate Using Fridericia's Method (QTcF) | 0.9 msec | Standard Error 2.4 |
Secondary
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.
Time frame: From Baseline to Day 29 ± 2
Population: Only subjects in Group 1 received CBP-307.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) | 543 h*ng/mL | Geometric Coefficient of Variation 24.4 |
Secondary
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.
Time frame: From Baseline to Day 29 ± 2
Population: Only subjects in Group 1 received CBP-307.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) | 237 h*ng/mL | Geometric Coefficient of Variation 21.8 |
Secondary
Categorical Outliers for HR
For categorical outliers, decrease in HR from predose baseline \>25% to an HR \<50 bpm will be determined.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Group 1 | Categorical Outliers for HR | 0 Participants |
| Investigational Group 2A+2B | Categorical Outliers for HR | 1 Participants |
Secondary
Categorical Outliers for PR
For categorical outliers, increase in PR from predose baseline \>25% to a PR \> 200 msec will be determined.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Group 1 | Categorical Outliers for PR | 0 Participants |
| Investigational Group 2A+2B | Categorical Outliers for PR | 0 Participants |
Secondary
Categorical Outliers for QRS
For categorical outliers, increase in QRS from predose baseline \>25% to a QRS \>120 msec will be determined.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Group 1 | Categorical Outliers for QRS | 0 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QRS | 0 Participants |
Secondary
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.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Investigational Group 1 | Categorical Outliers for QTcF | QTcF >450 and ≤480 msec | 1 Participants |
| Investigational Group 1 | Categorical Outliers for QTcF | Change-from-baseline QTcF >30 and ≤60 ms | 1 Participants |
| Investigational Group 1 | Categorical Outliers for QTcF | QTcF > 500 ms | 0 Participants |
| Investigational Group 1 | Categorical Outliers for QTcF | Change-from-baseline QTcF >60 ms | 0 Participants |
| Investigational Group 1 | Categorical Outliers for QTcF | QTcF > 480 and ≤500 ms | 0 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QTcF | Change-from-baseline QTcF >60 ms | 1 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QTcF | QTcF >450 and ≤480 msec | 3 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QTcF | QTcF > 480 and ≤500 ms | 0 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QTcF | Change-from-baseline QTcF >30 and ≤60 ms | 2 Participants |
| Investigational Group 2A+2B | Categorical Outliers for QTcF | QTcF > 500 ms | 0 Participants |
Secondary
Change-from-baseline Heart Rate (HR)
Change from Baseline in heart rate (HR).
Time frame: From Baseline at Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Change-from-baseline Heart Rate (HR) | -3.2 beats/min | Standard Error 0.98 |
| Investigational Group 2A+2B | Change-from-baseline Heart Rate (HR) | -1.3 beats/min | Standard Error 0.96 |
Secondary
Change-from-baseline PR
Change from Baseline in PR.
Time frame: From Baseline at Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Change-from-baseline PR | 4.5 msec | Standard Error 2.58 |
| Investigational Group 2A+2B | Change-from-baseline PR | -0.3 msec | Standard Error 2.51 |
Secondary
Change-from-baseline QRS
Change from Baseline in QRS.
Time frame: From Baseline at Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Change-from-baseline QRS | 0.1 msec | Standard Error 0.84 |
| Investigational Group 2A+2B | Change-from-baseline QRS | -0.5 msec | Standard Error 0.81 |
Secondary
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.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Flat | 0 Participants |
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Notched (+) | 0 Participants |
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Biphasic | 0 Participants |
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Normal (-) | 0 Participants |
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Notched (-) | 0 Participants |
| Investigational Group 1 | Frequency of Treatment-emergent Changes of T-wave Morphology | Inverted | 1 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Notched (-) | 0 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Flat | 2 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Normal (-) | 0 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Notched (+) | 0 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Inverted | 9 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of T-wave Morphology | Biphasic | 2 Participants |
Secondary
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.
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Group 1 | Frequency of Treatment-emergent Changes of U-wave Presence | 0 Participants |
| Investigational Group 2A+2B | Frequency of Treatment-emergent Changes of U-wave Presence | 0 Participants |
Secondary
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
Time frame: From Baseline to Day 29 ± 2
Population: Only subjects in Group 1 received CBP-307.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Investigational Group 1 | Incidence and Severity of Adverse Event (AE) | Overall | 12 participants |
| Investigational Group 1 | Incidence and Severity of Adverse Event (AE) | Serious | 0 participants |
| Investigational Group 1 | Incidence and Severity of Adverse Event (AE) | Leading to Discontinuation | 1 participants |
| Investigational Group 1 | Incidence and Severity of Adverse Event (AE) | Leading to Death | 0 participants |
Secondary
Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax) will be analyzed as a pharmacokinetic (PK) parameter.
Time frame: From Baseline to Day 29 ± 2
Population: Only subjects in Group 1 received CBP-307.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Maximum Observed Concentration (Cmax) | 13.5 ng/mL | Geometric Coefficient of Variation 22 |
Secondary
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
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Placebo-corrected Change-from-baseline HR | -1.9 beats/min | Standard Error 1.37 |
Secondary
Placebo-corrected Change-from-baseline PR
Placebo-corrected change-from-baseline PR based on Change-from-baseline PR reported in Outcome Measure 3
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Placebo-corrected Change-from-baseline PR | 4.8 msec | Standard Error 3.6 |
Secondary
Placebo-corrected Change-from-baseline QRS
Placebo-corrected change-from-baseline QRS based on Change-from-baseline QRS reported in Outcome Measure 4
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Placebo-corrected Change-from-baseline QRS | 0.6 msec | Standard Error 1.17 |
Secondary
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
Time frame: From Baseline to Day 16
Population: Per protocol, approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. That is to say, the placebo group is consist of Group 2A+Group 2B. The aim is to assess the ECG effect of CBP-307 versus placebo (CBP-307 in Group 1 versus placebo in Groups 2A and 2B).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Investigational Group 1 | Placebo-corrected Change-from-baseline QTcF | 0.6 msec | Standard Error 3.44 |
Secondary
Time of the Maximum Observed Concentration (Tmax)
Time of the maximum observed concentration (tmax) will be analyzed as a pharmacokinetic (PK) parameter.
Time frame: From Baseline to Day 29 ± 2
Population: Only subjects in Group 1 received CBP-307.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Investigational Group 1 | Time of the Maximum Observed Concentration (Tmax) | 3.02 h |