A Study of JPH034 in Healthy Adult Participants
Purpose
This study is designed to evaluate the safety, tolerability, and PK of JPH034 and identify side effects that occur in healthy participants between the ages of 18 and 50 years. Participants enrolling in the trial will be randomly assigned to receive JPH034 or placebo. Participants in the in single-ascending dose (SAD) cohorts will receive treatment once, and one group of participants will receive treatment a second time to study the effects of food. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety. Blood tests will be performed to measure how much JPH034 and its major metabolite (M1) gets into the bloodstream and how long it stays in the body.
Condition
- Health Adult Subjects
Eligibility
- Eligible Ages
- Between 18 Years and 50 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Age 18 to 50 years, inclusive, at the time of Screening. 2. Body mass index (BMI) ≥ 18.5 and ≤ 34 kg/m2 at Screening and Check-in. Sex and Contraceptive/Barrier Requirements 3. Females who are not pregnant or breastfeeding, agree to refrain from donating eggs during the study intervention period and for at least 30 days after the last dose of study intervention, and who meet one of the following conditions: 1. Postmenopausal (no menses for 12 months, without an alternative medical cause; Section 10.2.1), or 2. Permanent infertility (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or 3. Agree to abstain from heterosexual intercourse or to use a highly effective method of contraception (listed in Section 10.2.2) during the study intervention period and for at least 30 days after the last dose of study intervention. 4. Females with a negative serum pregnancy test at Screening and a negative urine pregnancy test at Check-in (within 24 hours before the first dose of study intervention). 5. Males who agree to the following conditions during the study intervention period and for at least 30 days after the last dose of study intervention: 1. Refrain from donating sperm and 2. Use one of the following forms of contraception: - Abstinence from heterosexual intercourse or - Condom if partner is a woman of CBP (defined in Section 10.2.1), plus highly effective method of contraception (listed in Section 10.2.2) if partner is a woman of CBP who is not currently pregnant. 6. Willing and able to provide voluntary, written informed consent to participate in the study. 7. Able to communicate well with the Investigator and/or study site personnel and to comply with the requirements of the entire study. 8. Negative drug/alcohol testing at Screening and Check-in. 9. Vital signs (after semi-recumbent for at least 5 minutes) that are within the following ranges at Screening and Check-in. If not within the stated ranges, they must be without clinical significance as determined by the Investigator. 1. Systolic BP, 90 to 140 mmHg, inclusive 2. Diastolic BP, 50 to 90 mmHg, inclusive 3. Heart rate (HR), > 45 to ≤ 100 bpm 10. Normal renal function, defined as eGFR > 90 mL/min at Screening; an Investigator can determine based on clinical judgment whether a lower rate can be accepted based on the muscle composition of the participants.
Exclusion Criteria
- History or presence of cardiovascular, respiratory, hepatic, renal, GI, endocrinological, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. 2. History of any active infection within 14 days of dosing with study intervention, if deemed clinically significant by the Investigator and Sponsor. 3. Any acute illness within 30 days prior to dosing with study intervention. 4. Clinically significant (as determined by the Investigator) abnormal laboratory test results, including, but not limited to, lipase, amylase, alkaline phosphatase, WBC count, or platelets, at Screening and Check-in. Note: Alkaline phosphatase, WBC count, and platelets must be within normal limits at Screening and Check-in. 5. Concurrent conditions that could interfere with safety and/or tolerability measurements, as determined by the Investigator or designee. 6. Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of JPH034. 7. History (within 2 years prior to the first dose of study intervention) of moderate or severe use disorder for any substance other than caffeine (based on DSM-5 criteria). 8. History of a major psychiatric disorder, ongoing suicidal ideations, or endorsement of suicidal ideation or behavior based on the C-SSRS at Screening. 9. Reduced sense of taste, as assessed by taste strips at Screening. 10. QTcF > 450 msec for males or > 470 msec for females observed at Screening or Check-in. 11. History or presence of any type of arrhythmia or irregular heartbeat. 12. Long QT syndrome or a history of cardiac disease. 13. Potassium or magnesium outside the normal range at Screening or Check-in (potassium normal range = 3.6-5.2 mEq/L; magnesium normal range = 1.9-2.7 mg/dL). 14. Use of any drug known to prolong the QT interval within 4 weeks prior to study. 15. ALT or AST > 1.5 × ULN at Screening or Check-in. 16. Total bilirubin > 1.5 × ULN at Screening or Check-in. For participants with known Gilbert's syndrome these criteria only apply if total bilirubin > 1.5 × ULN as long as direct bilirubin is ≤ 1.5 × ULN. 17. Current or chronic history of liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, steatotic liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the Investigator. 18. Use of prescription or non-prescription medications within 14 days or 5 half-lives, whichever is longer, before the first dose of study intervention. 19. Exposure to any investigational agent within 5 half-lives or 30 days, whichever is longer, prior to Screening. 20. Diagnosis of or positive Screening result for HCVAb, or HIV-1 or HIV-2. 21. Diagnosis of or positive Screening result for current or previous natural hepatitis B infection. Results indicative of vaccine-induced immunity (negative HBsAg and HBcAb plus positive HBsAb) will not be exclusionary. 22. Positive COVID-19 test. 23. Positive or indeterminate IGRA (QuantiFERON®-TB Gold Plus [QFT-Plus]) TB test. 24. Known history of allergy to JPH034 or other related drugs or their components. 25. Any food allergy, intolerance, restriction, or special diet that, in the opinion of the Investigator or designee, could contraindicate the participant's participation in the study. 26. Unable to ingest an entire high-fat/high-calorie meal. 27. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days prior to Screening. 28. Plasma donation within 7 days of Screening. 29. Unable or unwilling to cooperate with site staff for any reason. 30. Study site employees, immediate family members of a study site employee, or anyone whose participation in the study would create a conflict of interest for a study site employee.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 1. SAD Cohort 1 - 20mg |
Single dose N = 6 JPH034: 2 Placebo |
|
|
Experimental 2. SAD Cohort 2 - 40mg |
Single dose N = 6 JPH034: 2 Placebo |
|
|
Experimental 3. SAD Cohort 3 - 80mg |
Single dose N = 6 JPH034: 2 Placebo |
|
|
Experimental 4. SAD Cohort 4 -160mg |
Single dose N = 6 JPH034: 2 Placebo |
|
|
Experimental 5. SAD Cohort 5 - TBD |
Single dose N = 6 JPH034: 2 Placebo |
|
|
Experimental 6. SAD Food Effect - TBD |
Single dose N = 6 JPH034: 2 Placebo |
|
Recruiting Locations
Dilworth, Minnesota 56529
More Details
- Status
- Recruiting
- Sponsor
- J-Pharma Co., Ltd.
Detailed Description
This is a Phase 1, single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and PK and PD of single-ascending doses of JPH034 and its major metabolite (M1) in healthy adult participants. In addition, an unblinded pilot food effect (FE) evaluation is planned to characterize the effect of food (high-fat meal vs fasted conditions) on the single-dose PK of JPH034. Participants will be randomly allocated to treatment cohorts (JPH034 or placebo) at the dose level open at the time of enrollment; randomization (prior to dosing on Day 1) will be managed using a sequential list. Participants will be permitted to participate in only 1 dose cohort of the study. Single-Ascending Dose: The first SAD cohort will receive a dose of 20 mg JPH034 or placebo, and subsequent cohorts will receive anticipated escalating doses of JPH034 or placebo. Sentinel dosing will be utilized for all SAD cohorts. Eligible participants will check into the clinic on Day -1 and will remain confined through the 48-hour PK collection on Day 3. On Day 1, participants will receive a single dose of study intervention under fasted conditions. Following completion of the observation period for the last participant in each cohort, the Safety Review Committee (SRC) will review available data from the observation period (including TEAEs, laboratory results, vital signs, ECGs, and PK data) and any cumulative data from prior cohorts. The observation period will be 7 days after administration of study intervention. The SRC may review unblinded data as necessary. Pilot Food Effect: The FE evaluation will be performed at a safe dose level as determined by the SRC. The effect of food on the systemic exposure of JPH034 is not known; therefore, the SRC will consider safety associated with potentially higher exposures and select an appropriate dose for the FE evaluation accordingly. JPH034-treated participants (N = 6) from the selected SAD cohort will return for a pilot FE evaluation. Participants will undergo a washout prior to this FE evaluation (fasted dose on Day 1; fed dose on FE Day 1) for a minimum of 5 half-lives of JPH034. Participants will check into the clinic on FE Day -1 and will remain confined through the 48-hour PK collection on FE Day 3. On FE Day 1, participants will receive a single dose of JPH034 in a fed state (high-fat/high-calorie standard meal) following a minimum 10-hour overnight fast. Participants will have 30 minutes to ingest the entire meal, and the JPH034 dose will be administered 30 minutes after the start of the meal. Participants will then fast for at least 4 hours postdose. For the SAD and FE cohorts safety assessments, as well as blood samples and urine collection for PK analyses will be performed. Participants will return to the clinic for PK collections 72 and 96 hours after administration of study intervention (Days 4 and 5, respectively). Seven to 9 days after administration of study intervention, participants will attend a follow-up visit.