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Trial record 1 of 1 for:    CVN766
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Phase 1 SAD/MAD Study of CVN766 in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT05105243
Recruitment Status : Not yet recruiting
First Posted : November 3, 2021
Last Update Posted : November 3, 2021
Sponsor:
Information provided by (Responsible Party):
Cerevance

Brief Summary:
Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN766 in Healthy Subjects

Condition or disease Intervention/treatment Phase
Safety Issues Tolerance Drug: CVN766 Phase 1

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

For the single-dose regimen, approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 subjects randomized to CVN766 or placebo, whereby 6 subjects will receive a single oral dose of CVN766 suspension, and 2 subjects will receive a matching placebo suspension under overnight fasted conditions.

For the multiple-dose regimen, approximately 24 healthy male and female subjects age 18 to 50 years old will be enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. The dose levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose cohorts M1 through M3, respectively.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blind. placebo-controlled.
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN766 in Healthy Subjects
Estimated Study Start Date : January 2022
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : October 2022

Arm Intervention/treatment
Active Comparator: SAD Cohort 1
Each dose cohort: 8 subjects (6 active:2 placebo). 5 mg
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Active Comparator: SAD Cohort 2
Each dose cohort: 8 subjects (6 active:2 placebo). 15 mg.
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Active Comparator: SAD Cohort 3
Each dose cohort: 8 subjects (6 active:2 placebo). 45 mg.
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Active Comparator: SAD Cohort 4
Each dose cohort: 8 subjects (6 active:2 placebo). 125 mg
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Placebo Comparator: SAD Cohort 5
Each dose cohort: 8 subjects (6 active:2 placebo). 250 mg.
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Active Comparator: MAD Cohort 1
Each dose cohort: 8 subjects (6 active:2 placebo). 45mg
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Placebo Comparator: MAD Cohort 2
Each dose cohort: 8 subjects (6 active:2 placebo). 125 mg.
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist

Placebo Comparator: MAD Cohort 3
Each dose cohort: 8 subjects (6 active:2 placebo). 250 mg.
Drug: CVN766
highly selective orexin-1 receptor (Ox1R) antagonist




Primary Outcome Measures :
  1. Evaluation of Adverse Events [ Time Frame: Baseline through 14 days post final dose ]
    Occurrence of all adverse events from signing of informed consent through end of study treatment.

  2. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    RBC

  3. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post final dose ]
    typanic body temperature

  4. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QT interval

  5. Evaluation of BMI [ Time Frame: Baseline through 14 days post final dose ]
    Weight and Height will be combined to calculate BMI using the following formula: BMI = weight (kg)/[height (m)]2

  6. Evaluation Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    ALT

  7. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    pH

  8. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post final dose ]
    Respiration Rate

  9. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post final dose ]
    Pulse Rate

  10. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post final dose ]
    Blood Pressure (both systolic and diastolic)

  11. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    WBC with differential

  12. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    Hemoglobin

  13. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    Hematocrit

  14. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    PT/INR

  15. Evaluation of Hematology [ Time Frame: Baseline through 14 days post final dose ]
    Platelets

  16. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QTc

  17. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - PR

  18. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - RR

  19. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QRS

  20. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QT

  21. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QTcF

  22. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post final dose ]
    Standard 12-lead ECG - QTcB

  23. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Albumin

  24. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Alkaline phosphatase

  25. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Lipase

  26. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    AST

  27. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Total bilirubin

  28. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Direct bilirubin

  29. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Total Protein

  30. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Creatinine

  31. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Blood urea nitrogen

  32. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Creatine kinase

  33. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    GGT

  34. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Potassium

  35. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Sodium

  36. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Glucose

  37. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Chloride

  38. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Bicarbonate

  39. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post final dose ]
    Calcium

  40. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    specific gravity

  41. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    protein

  42. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    glucose

  43. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    blood

  44. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    nitrite

  45. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post final dose ]
    Microscopic Analysis (only if positive dipstick results): RBC/high power field, WBC/high power field, Epithelial cells, casts


Secondary Outcome Measures :
  1. Plasma Concentration (AUC) of CVN766 [ Time Frame: SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) ]
    To evaluate the pharmacokinetics of single and multiple doses of CVN766 Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 24hours (AUC0-24)

  2. Plasma Concentration (Cmax) of CVN766 [ Time Frame: SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) ]
    To evaluate the pharmacokinetics of single and multiple doses of CVN766. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax)

  3. Food effect by measurement of plasma PK (Cmax) [ Time Frame: Baseline through 14 days post-dose ]
    Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.

  4. Food effect by measurement of plasma PK (AUC) [ Time Frame: Baseline through 14 days post-dose ]
    Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.


Other Outcome Measures:
  1. DNA isolation and genotyping [ Time Frame: Day 1 ]

    Drug metabolic enzyme and transporter polymorphisms that may contribute to variability in CVN766 will be reported.

    Single-dose -pre-dose Multi-dose

    -pre-dose


  2. RNA isolation and genotyping [ Time Frame: Day 1 and Day 7 ]

    Single-dose -pre-dose, 8 and 24 hours post dose Multi-dose

    -pre-dose, 8 and 24 hours post dose




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject eligibility is determined according to the following criteria prior to entry into the study:

    1. In the investigator's opinion, the subject can understand and sign the Informed Consent Form and comply with all protocol requirements.
    2. The subject is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time of ICF.
    3. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive at Screening.
    4. A male subject who is nonsterilized* and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing the ICF throughout the study and for 12 weeks after the last dose.

      *Definitions and acceptable methods of contraception are defined in Section 9.1.9 Contraception and Pregnancy Avoidance Procedure, and reporting responsibilities are defined in Section 9.1.10 Pregnancy.

    5. A female subject of childbearing potential who complies with contraception requirements* or a female with no childbearing potential, defined as the subject has been surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and FSH>40 IU/L).

Exclusion Criteria:Any subject who meets any of the following criteria will not qualify for entry into the study:

  1. Subject has received any investigational compound within 30 days prior to the first dose of study medication or within 5 half-lives, whichever is greater.
  2. Subject is a study site employee or an immediate family member of a study site employee.
  3. Subject has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious allergy, full-body allergic skin rash (including hives), psychiatric disorder, or other abnormality that may impact the ability of the subject to participate or potentially confound the study results.
  4. There is any finding in the subject's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a similar drug in the same class or that might interfere with the conduct of the study
  5. Subject has a known hypersensitivity to any component of the formulation of CVN766.
  6. Subject has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day -1).
  7. Subject has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
  8. Subject has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table as listed in Table 3: Excluded Medications and Dietary Products.
  9. Male subjects who do not agree to all the following rules: when sexually active with a female partner(s) of childbearing potential during the study, and for 12 weeks after the last dose of study drug: a) must use an acceptable method of birth control (condom or surgical sterilization) and b) refrain from sexual activity with female partners who do not use an acceptable method of birth control. Barrier contraception (condom) must be used by all-male subjects who were not surgically sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from sperm donation during the study and until 12 weeks after the last dose of study drug.
  10. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova during the study or 30 days after the last dose of the study drug. Women of childbearing potential must agree to practice an acceptable method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence).

    *Definitions and acceptable methods of contraception are defined in Section 9.1.9, Contraception and Pregnancy Avoidance Procedure, and reporting responsibilities are defined in Section 9.1.10, Pregnancy.

  11. Subject has previously had a seizure or convulsion (lifetime, with the exception of febrile seizures), including absence seizure.
  12. Subject has current o recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption [e.g., bariatric surgery or bowel resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent [i.e., more than once per week] occurrence of heartburn).
  13. Subject has a history of cancer or other malignancy, except for basal cell carcinoma or squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1.
  14. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a human immunodeficiency virus infection at Screening.
  15. Subject who regularly use nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). Casual user may participate but must agree to refrain from the time of Screening for the duration of the study or a positive urine cotinine test at Inpatient Check-in (Day 1).
  16. Subject has poor peripheral venous access (defined as more than three failed attempts to cannulate.
  17. Subject has donated or lost 450 mL or more of their blood volume (including plasmapheresis) or had a transfusion of any blood product within 45 days prior to Day 1.
  18. Subject has an abnormal (CS) ECG at Screening or Inpatient Check-in (Day -1). Entry of any subject with an abnormal (NCS) ECG must be approved and documented by signature by the Investigator or medically qualified sub-investigator.
  19. Subject has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 40 to 90 mm Hg for diastolic, confirmed with repeat per PI discretion, at the Screening Visit or Inpatient Check-in (Day -1).
  20. Subject has a resting heart rate outside the range of 40 to 100 bpm, confirmed with repeat per PI discretion, at the Screening Visit or Inpatient Check-in (Day -1).
  21. Subject has a QT interval with Fridericia's correction method (QTcF) >450 ms (males) or >470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing at the Screening Visit or Inpatient Check-in (Day -1) Visit.
  22. Subject has abnormal Screening or Inpatient Check-in (Day -1) laboratory values that suggest a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 the ULN, confirmed with one repeat testing.
  23. Subject has a risk of suicide according to the investigator's clinical judgment or has made a suicide attempt in the previous 2 years.

7.3 Excluded Medications and Dietary Products

-

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Responsible Party: Cerevance
ClinicalTrials.gov Identifier: NCT05105243    
Other Study ID Numbers: CVN-766
First Posted: November 3, 2021    Key Record Dates
Last Update Posted: November 3, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cerevance:
PK
Efficacy