A Safety, Tolerability, and Pharmacokinetic Study of NIP292 in Healthy Normal Subjects

NCT04720443 | Completed Phase 1 FDA Drug

• 1 other identifier: NIP292-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to evaluate the safety and tolerability of single ascending and multiple ascending oral doses of NIP292 tablets administered following an overnight fast in healthy adult subjects.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (6)

• To evaluate the incidence, potential significance, and clinical importance of adverse events (AE) after single dose of NIP292 in 48 healthy subject.

  The AEs developed during or after the study treatment (as treatment-emergent adverse event \[TEAE\]) will be summarized by preferred term, system organ class, severity, and relationship to the investigational product.

  31 days

• To evaluate the incidence, potential significance, and clinical importance of adverse events (AE) after multipe dose of NIP292 in 24 healthy subject.

  The AEs developed during or after the study treatment (as treatment-emergent adverse event \[TEAE\]) will be summarized by preferred term, system organ class, severity, and relationship to the investigational product.

  37 days

• The change of Clinical Laboratory Tests

  Descriptive statistics of absolute values and changes from baseline will be summarized by dose/regimen and time. Laboratory abnormalities will be tabulated by time.

  31 days in SAD

• The change of Clinical Laboratory Tests

  Descriptive statistics of absolute values and changes from baseline will be summarized by dose/regimen and time. Laboratory abnormalities will be tabulated by time.

  37 days in MAD

• Electrocardiogram (ECG)

  Changes from baseline for the ECG parameters (i.e., QT, heart rate, QTcF, PR and QRS) will be summarized by dose/regimen and time. The number (%) of subjects with maximum post-dose QTcF values and maximum increases from baseline will be tabulated by regimen.

  31 days in SAD

• Electrocardiogram (ECG)

  Changes from baseline for the ECG parameters (i.e., QT, heart rate, QTcF, PR and QRS) will be summarized by dose/regimen and time. The number (%) of subjects with maximum post-dose QTcF values and maximum increases from baseline will be tabulated by regimen.

  37 days in MAD

Secondary Outcomes (7)

• To characterize the maximum plasma concentration(Cmax) of NIP292 tablets in 48 healthy adult subjects.

  31 days

• To characterize the time to maximum plasma concentration (Tmax) of NIP292 tablets in 48 healthy adult subjects.

  31 days

• To characterize the time to area under the concentration-time curve from hour 0 to last postdose(AUC0-last) of NIP292 tablets in 48 healthy adult subjects.

  31 days

• To characterize the maximum plasma concentration(Cmax) of NIP292 tablets in 24 healthy adult subjects.

  37 days

• To characterize the time to maximum plasma concentration (Tmax) of NIP292 tablets in 24 healthy adult subjects.

  37 days

Study Arms (7)

SAD Part 1 Cohort 1

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet at 10 mg) or placebo. In each cohort, to mitigate any unforeseen safety issues, the first 2 subjects (1 active + 1 placebo) will be admitted and dosed, and at least 48 hours apart from the other 6 subjects. The remaining 6 subjects of each cohort will be dosed after review of the safety data of the first 2 subjects.

Drug: NIP292 tablet

SAD Part 1 Cohort 2

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet at 30 mg) or placebo. In each cohort, to mitigate any unforeseen safety issues, the first 2 subjects (1 active + 1 placebo) will be admitted and dosed, and at least 48 hours apart from the other 6 subjects. The remaining 6 subjects of each cohort will be dosed after review of the safety data of the first 2 subjects.

Drug: NIP292 tablet

SAD Part 1 Cohort 3

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet at 100mg) or placebo. In each cohort, to mitigate any unforeseen safety issues, the first 2 subjects (1 active + 1 placebo) will be admitted and dosed, and at least 48 hours apart from the other 6 subjects. The remaining 6 subjects of each cohort will be dosed after review of the safety data of the first 2 subjects.

Drug: NIP292 tablet

SAD Part 1 Cohort 4

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet at 300 mg) or placebo. In each cohort, to mitigate any unforeseen safety issues, the first 2 subjects (1 active + 1 placebo) will be admitted and dosed, and at least 48 hours apart from the other 6 subjects. The remaining 6 subjects of each cohort will be dosed after review of the safety data of the first 2 subjects.

Drug: NIP292 tablet

SAD Part 1 Cohort 5

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet at 500 mg)or placebo. In each cohort, to mitigate any unforeseen safety issues, the first 2 subjects (1 active + 1 placebo) will be admitted and dosed, and at least 48 hours apart from the other 6 subjects. The remaining 6 subjects of each cohort will be dosed after review of the safety data of the first 2 subjects.

Drug: NIP292 tablet

MAD Part 2 Cohort 1

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet dosage 1) or placebo. All subjects will receive either NIP292 or placebo on an empty stomach for 7 days (from Day 1 to Day 7), and dosing frequency will be identical and either QD, Q12H, or Q8H (depending on the observed PK data in Part 1). Two dose levels (dose 1 and dose 2) proposed for MAD part will be determined based on the doses evaluated in SAD part.

Drug: NIP292 tablets

MAD Part 2 Cohort 2

EXPERIMENTAL

Eight subjects will be randomized at a ratio of 3:1 in each cohort to receive either NIP292 (oral tablet dosage 2) or placebo. All subjects will receive either NIP292 or placebo on an empty stomach for 7 days (from Day 1 to Day 7), and dosing frequency will be identical and either QD, Q12H, or Q8H (depending on the observed PK data in Part 1). Two dose levels (dose 1 and dose 2) proposed for MAD part will be determined based on the doses evaluated in SAD part.

Drug: NIP292 tablets

Interventions

NIP292 tablet DRUG

NIP292 (oral tablet at 10 mg) or placebo

SAD Part 1 Cohort 1

NIP292 tablets DRUG

NIP292 (oral tablet at dosage 1) or placebo

MAD Part 2 Cohort 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female (non-childbearing potential) subjects between age 18 and 55 years (inclusive), in general good health without clinically significant abnormalities.
• Female subjects of non-childbearing potential will be authorized to participate in this study if at least one of the following criteria are met:
• Surgical sterilization (e.g., hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, but excluding bilateral tubal occlusion);
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state (with a single repeat permitted if deemed necessary by the investigator); and β-human chorionic gonadotropin (β-HCG) is negative at screening and the admission.
• Body mass index (BMI) of 18-32 kg/m2 (inclusive), and a total body weight \>50 kg (110 lb).
• Clinical laboratory values within the normal limits as defined by the clinical laboratory. Of note, individual values out of normal range can be accepted if judged as not clinically significant by the investigator. Repeat assessment can be conducted at the discretion of the investigator or delegate.
• Subjects who are willing and able to comply with the prescribed protocol treatment and evaluations.
• Subjects must provide signed written informed consent prior to any study-specific procedures.

You may not qualify if:

• Subjects with any of the following characteristics or conditions will not be included in the study:
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies).
• History of drug abuse in the past 5 years, or a positive urine drug test at screening or the admission.
• History of excessive alcohol intake exceeding 14 drinks/week (1 drink = 5 ounces \[150 mL\] of wine, or 12 ounces \[360 mL\] of beer, or 1.5 ounces \[45 mL\] of hard liquor) within 6 months of screening, or a positive alcohol breath test at screening or the admission.
• Current smoker, or difficulty abstaining from smoking for the duration of study confinement.
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.
• Use of prescription or nonprescription drugs or dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication; however, limited use of nonprescription medications that are not believed to affect the overall results of the study may be permitted on a case by case basis following approval by the investigator and the Sponsor.
• Previous participation in this study; subjects can only be randomized and receive the study medication in 1 of the 2 parts in this study.
• Any condition possibly affecting drug absorption per the principal investigator's discretion (e.g., gastrectomy).
• Screening supine systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. If SBP ≥140 mmHg or DBP ≥90 mmHg, the blood pressure assessment should be repeated 2 more times and the average of the 3 blood pressure values should be used to determine the subject's eligibility.
• Screening supine 12-lead ECG demonstrating a QTcF (using Fridericia's formula, QTcF = QT/RR1/3) interval \>450 msec for males or \>470 msec for females,or a QRS interval \>120 msec. If QTcF \>450 msec or QRS \>120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the subject's eligibility.
• Subjects with history of hepatitis, or positive result at screening for hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), hepatitis C antibody (HCVAb), or human immunodeficiency virus antibody (HIVAb).
• Pregnant female subjects; breastfeeding female subjects; male subjects able to father children who are unable to use a highly effective method of contraception for the duration of the study and for at least 90 days after the last dose of study medication.
• Blood donation (excluding plasma donations) of approximately 450 mL or more within 60 days prior to the first dose of study medication.
• History of sensitivity to heparin or heparin induced thrombocytopenia (if heparin is used to flush intravenous catheters used during serial blood collections).

Sponsors & Collaborators

• The National Institutes of Pharmaceutical R&D Co. Ltd, China: lead

Study Sites (1)

PAREXEL International

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2020
• First Posted: January 22, 2021
• Study Start: November 22, 2019
• Primary Completion: July 14, 2022
• Study Completion: July 14, 2022
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

US (1)