Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CHK-336 in Healthy Volunteers

NCT ID: NCT05367661

Last Updated: 2023-11-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-08
• Study Completion Date: 2023-04-19

Brief Summary

This study is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic effects of an investigational drug (CHK-336) when administered to healthy volunteers.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: Healthy Volunteers: Single ascending doses

Six dose groups ranging from 15mg to 500mg, under fasting condition.

Group Type: EXPERIMENTAL

CHK336

Intervention Type: DRUG

Tablet

Placebo

Intervention Type: DRUG

Tablet

Part A: Healthy Volunteer: Single Ascending dose under fed condition

60mg under fed condition.

Group Type: EXPERIMENTAL

CHK336

Intervention Type: DRUG

Tablet

Part A: Otherwise Healthy volunteer with Class I or Class II obesity, Single Ascending dose

125mg, under fasting condition.

Group Type: EXPERIMENTAL

CHK336

Intervention Type: DRUG

Tablet

Placebo

Intervention Type: DRUG

Tablet

Part B: Healthy Volunteers: Multiple Ascending doses

5 dose groups with doses ranging from 30mg to 500mg. Given daily for 14 days, under fasting condition.

Group Type: EXPERIMENTAL

CHK336

Intervention Type: DRUG

Tablet

Placebo

Intervention Type: DRUG

Tablet

Interventions

CHK336

Tablet

Intervention Type: DRUG

Placebo

Tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female adults18 to 45years old, inclusive, at the time of consent.

2. Body mass index (BMI) between 19 and 32 kg/m2, inclusive, (between 30.0 and < 40.0 kg/m2 for SAD Cohort A8) at screening.

3. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. All participants (male or female) who are of childbearing potential must agree to use highly effective contraception during the study. Female participants must continue to use highly effective contraception during the study for 30 days after the last dose of study drug. Female participants should not donate oocytes during this time. Male participants with female partners of childbearing potential must continue to use highly effective contraception during the study and for 90 days after the last dose of study drug. Male participants must agree not to donate sperm during this time. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and Day -3 as well as a negative urine pregnancy test at Day 1 (predose). WOCBP must agree to undergo a pregnancy test during the study

5. Female participants not of childbearing potential must be either surgically sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or postmenopausal, defined as no menses for 12 months without an alternative medical cause, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the central laboratory's ranges.

6. Willing and able to provide informed consent and comply with all study visits and procedures including overnight stays in the clinic

7. Willing and able to comply with a pre-specified diet at least 72 hours prior to dose and throughout the study.

8. Negative urine drug, tobacco, and breath alcohol test result at screening and Day-3.

9. Have not used any nicotine-containing product within 3 months prior to the first study drug administration and who are willing to abstain throughout the study.

Exclusion Criteria

1. Any significant medical history including but not limited to hypertension, diabetes, cardiovascular disease, hemolysis, red blood cell disorders, and/or with clinically significant screening results outside the normal range for laboratory testing, vital signs, medical history, electrocardiograms (ECGs), physical examination as deemed by the investigator. Reticulocytes must be within normal range at screening and prior to dosing. Red blood cell (RBC), hemoglobin, and hematocrit must be within 5% of normal range at screening and prior to dosing.

2. Evidence of chronic kidney disease (CKD) defined by an estimated glomerular filtration rate (eGFR) less than 80 mg/mL/1.73m2 based on the CKD epidemiology collaboration (EPI) equation or the presence of proteinuria at screening and prior to dosing.

3. Have any known malignancy or history of malignancy, except for basal cell skin cancer that has been treated and with no evidence of recurrence for at least 3 months prior to the first study drug administration.

4. History of liver disease, Gilbert's syndrome, or abnormal liver function test (AST, ALT, total bilirubin) above the normal reference range at screening and prior to dosing.

5. Any active infection or acute illness within 30 days prior to the first study drug administration.

6. Major surgery or significant traumatic injury occurring within 28 days prior to first dose of study drug. If major surgery occurred > 28 days prior to first dose of study drug, individual must have recovered adequately from any toxicity and/or complications from the intervention prior to the first dose of study drug.

7. Supine systolic blood pressure <90 or >140 mmHg, supine diastolic blood pressure <50 or >95 mmHg, pulse rate <40 or >100 beats per minute (bpm), or elevated body temperature (>38ºC) at screening and check-in

8. History or presence of a clinically significant ECG abnormalities and QTcF >450 ms for males and >470 ms for females, prior to dosing.

9. Positive serology tests for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).

10. Use of any prescription, vaccines, supplements/vitamins, or over-the counter medication (with the exception of oral contraceptives) within 7 days prior to the first study drug administration.

11. Treatment with another investigational product within 30 days prior to the first study drug administration or within the expected washout (~5 half-lives) of the investigational product

12. Prior exposure to CHK-336 (including Part A of this study).

13. History or presence of alcohol abuse or drug use within 30 days prior to the first study drug administration and throughout the study

14. Blood donation or significant blood loss within 60 days prior to the first study drug administration.

15. Pregnancy, intent to become pregnant during the course of the study, or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chinook Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States

Countries

United States

References

Cox JH, Boily MO, Caron A, Sheng T, Wu J, Ding J, Gaudreault S, Chong O, Surendradoss J, Gomez R, Lester J, Dumais V, Li X, Gumpena R, Hall MD, Waterson AG, Stott G, Flint AJ, Moore WJ, Lowther WT, Knight J, Percival MD, Tong V, Oballa R, Powell DA, King AJ. Characterization of CHK-336, A First-in-Class, Liver-Targeted, Small-Molecule Lactate Dehydrogenase Inhibitor for Hyperoxaluria Treatment. J Am Soc Nephrol. 2025 Apr 7;36(8):1535-1547. doi: 10.1681/ASN.0000000690.

Reference Type: DERIVED

PMID: 40193200 (View on PubMed)

Other Identifiers

CHK336-01

Identifier Type: -

Identifier Source: org_study_id