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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NIP292 tablet | Drug | NIP292 (oral tablet at 10 mg) or placebo |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| To characterize the maximum plasma concentration(Cmax) of NIP292 tablets in 48 healthy adult subjects. | PK parameters derived from plasma NIP292 concentration data following single oral doses: maximum plasma concentration(Cmax) | 31 days |
| To characterize the time to maximum plasma concentration (Tmax) of NIP292 tablets in 48 healthy adult subjects. |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
Subjects with any of the following characteristics or conditions will not be included in the study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PAREXEL International | Glendale | California | 91206 | United States |
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| 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. |
|
| 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. |
|
| 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. |
|
| NIP292 tablet |
| Drug |
NIP292 (oral tablet at 30 mg) or placebo |
|
| NIP292 tablet | Drug | NIP292 (oral tablet at 100 mg) or placebo |
|
| NIP292 tablet | Drug | NIP292 (oral tablet at 300 mg) or placebo |
|
| NIP292 tablet | Drug | NIP292 (oral tablet at 500 mg) or placebo |
|
| NIP292 tablets | Drug | NIP292 (oral tablet at dosage 1) or placebo |
|
| NIP292 tablets | Drug | NIP292 (oral tablet at dosage 2) or placebo |
|
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 |
PK parameters derived from plasma NIP292 concentration data following single oral doses: time to maximum plasma concentration (Tmax) |
| 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. | PK parameters derived from plasma NIP292 concentration data following single oral doses: area under the concentration-time curve from hour 0 to last postdose(AUC0-last) | 31 days |
| To characterize the maximum plasma concentration(Cmax) of NIP292 tablets in 24 healthy adult subjects. | PK parameters derived from plasma NIP292 concentration data following multiple oral doses: maximum plasma concentration (Cmax) | 37 days |
| To characterize the time to maximum plasma concentration (Tmax) of NIP292 tablets in 24 healthy adult subjects. | PK parameters derived from plasma NIP292 concentration data following multiple oral doses: time to maximum plasma concentration (Tmax) | 37 days |
| To characterize the area under the concentration-time curve from hour 0 to last postdose(AUC0-last) of NIP292 tablets in 24 healthy adult subjects. | PK parameters derived from plasma NIP292 concentration data following multiple oral doses:area under the concentration-time curve from hour 0 to last postdose(AUC0-last) | 37 days |
| To characterize the renal clearance of NIP292 tablets, if data permit | the urine PK parameters:renal clearance(CLr) | 37 days |
| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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