Study in Chinese Healthy Adults to Evaluate the Safety, Tolerability and Pharmacokinetics on ZSP1601, and the Effect of Food on ZSP1601 Pharmacokinetics

NCT03392779 | Completed Phase 1

• 1 other identifier: ZSP1601-16-01
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single- and multiple-oral doses of ZSP1601 on fasted condition, and characterize PK of ZSP1601 on an empty stomach (fasted condition) and following a high fat, high calorie meal (fed condition) in a 2-period, 2-sequence manner. The study will be conducted in 3 parts (Ascending single dose, multiple dose and food effect). Participants will receive either ZSP1601 or placebo .

Conditions

Nonalcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (7)

• Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses(single,multiple and food effect)of ZSP1601 and placebo.

  SAD Group: Up to 4 days, MAD: Up to 17days, FE group: Up to 11 days after first dose

• Concomitant Medication

  UP to 4, 17, 11 days for SAD, MAD, FE part respectively

• Clinical Laboratory Abnormalities(Blood routine test, serum biochemical test, conventional coagulation examinations, urine examination ) post dose of ZSP1601 and placebo.

  UP to 4, 17, 11 days for SAD, MAD, FE part respectively

• 12-lead ECG Abnormalities following oral dosing of ZSP1601 and placebo.

  UP to 4, 17, 11 days for SAD, MAD, FE part respectively

• Vital signs Abnormalities following oral dosing of ZSP1601 and placebo.

  UP to 4, 17, 11 days for SAD, MAD, FE part respectively

• Physical examination Abnormalities following oral dossing of ZSP1601 and placebo.

  UP to 4, 17, 11 days for SAD, MAD, FE part respectively

• Cardiac color ultrasound(UCG) Abnormalities following multiple oral doses of ZSP1601 and placebo.

  Screening, Day17

Secondary Outcomes (13)

• AUClast（AUC0-t）of ZSP1601

  UP to 2, 16, 9 days for SAD, MAD, FE part respectively

• AUCinf（AUC0-∞）of ZSP1601

  UP to 2, 16, 9 days for SAD, MAD, FE part respectively

• Cmax of ZSP1601

  UP to 2, 16, 9 days for SAD, MAD, FE part respectively

• Tmax of ZSP1601

  UP to 2, 16, 9 days for SAD, MAD, FE part respectively

• t1/2z of ZSP1601

  UP to 2, 16, 9 days for SAD, MAD, FE part respectively

Study Arms (9)

ZSP1601(single dose)-25 mg while fasted(Cohort 1)

EXPERIMENTAL

ZSP1601 25 mg /Placebo

Drug: ZSP1601 25 mg; Drug: Placebo 25mg

ZSP1601(single dose)-50 mg while fasted(Cohort 2)

EXPERIMENTAL

ZSP1601 50 mg/Placebo Enrollment into Cohort 2 will begin upon assurance of safety for Cohort 1.

Drug: ZSP1601 50 mg; Drug: Placebo 50 mg

ZSP1601(single dose)-100 mg while fasted(Cohort 3)

EXPERIMENTAL

ZSP1601 100 mg/Placebo Enrollment into Cohort 3 will begin upon assurance of safety for Cohort 2.

Drug: ZSP1601 100 mg; Drug: Placebo 100 mg

ZSP1601(single dose)-175 mg while fasted(Cohort 4)

EXPERIMENTAL

ZSP1601 175 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of safety for Cohort 3.

Drug: ZSP1601 175 mg; Drug: Placebo 175 mg

ZSP1601(single dose)-275 mg while fasted(Cohort 5,i.e.Group A)

EXPERIMENTAL

ZSP1601 275 mg/Placebo Enrollment into Cohort 5 will begin upon assurance of safety for Cohort 4.

Drug: ZSP1601 275 mg; Drug: Placebo 275 mg

ZSP1601(single dose)-350 mg while fasted(Cohort 6)

EXPERIMENTAL

ZSP1601 350 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of safety for Cohort 5.

Drug: ZSP1601 350 mg; Drug: Placebo 350mg

ZSP1601(food effect)-100 mg (Cohort FE)

EXPERIMENTAL

Period 1 (Day1 to Day4): Group A and Group B receive ZSP1601 100 mg/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day11): Group A and Group B receive ZSP1601 100 mg/Placebo under the fed or fasting condition ,respectively on Day8.

Drug: ZSP1601 100 mg; Drug: Placebo 100mg

ZSP1601(multiple doses)-50 mg (Cohort 7)

EXPERIMENTAL

50 mg ZSP1601 will be administrated while fasted or fed according to the results of Cohort FE ZSP1601 50 mg/Placebo for 14 Days.

Drug: ZSP1601 50 mg; Drug: Placebo 50 mg

ZSP1601(multiple doses)-100 mg (Cohort 8)

EXPERIMENTAL

Enrollment into Cohort 8 will begin upon assurance of safety for Cohort 7. ZSP1601 100 mg/Placebo for 14 Days.

Drug: ZSP1601 100 mg; Drug: Placebo 100 mg

Interventions

ZSP1601 25 mg DRUG

ZSP1601 tablet administered orally once daily under fasted condition

ZSP1601(single dose)-25 mg while fasted(Cohort 1)

Placebo 25mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

ZSP1601(single dose)-25 mg while fasted(Cohort 1)

ZSP1601 50 mg DRUG

ZSP1601 tablet administered orally once daily under fasted condition

ZSP1601(single dose)-50 mg while fasted(Cohort 2)

Placebo 50 mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

ZSP1601(single dose)-50 mg while fasted(Cohort 2)

ZSP1601 100 mg DRUG

ZSP1601 tablets administered orally once daily in the fasting state

ZSP1601(single dose)-100 mg while fasted(Cohort 3)

Placebo 100 mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

ZSP1601(single dose)-100 mg while fasted(Cohort 3)

ZSP1601 175 mg DRUG

ZSP1601 tablets administerekd orally once daily under fasted condition

ZSP1601(single dose)-175 mg while fasted(Cohort 4)

Placebo 175 mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

ZSP1601(single dose)-175 mg while fasted(Cohort 4)

ZSP1601 275 mg DRUG

ZSP1601 tablets administered orally once daily in the fasting state

ZSP1601(single dose)-275 mg while fasted(Cohort 5,i.e.Group A)

Placebo 275 mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

ZSP1601(single dose)-275 mg while fasted(Cohort 5,i.e.Group A)

ZSP1601 350 mg DRUG

ZSP1601 tablets administered orally once daily under fasted condition

ZSP1601(single dose)-350 mg while fasted(Cohort 6)

Placebo 350mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

ZSP1601(single dose)-350 mg while fasted(Cohort 6)

Placebo 100mg DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition

ZSP1601(food effect)-100 mg (Cohort FE)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects are required to meet the following criteria in order to be included in the trial:
• Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects(including adverse events) of the trial prior to enrollment.
• Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• Subjects(including partners)have no gestation plans and must use reliable methods of contraception during the study and until 6 months following the last dose of investigational product.
• Males and female subjects between 18-50 years (Both inclusive).
• Body weight is no less than 50kg in males and no less than 45kg in females.Body mass index (BMI) 18≤BMI≤28 kg/m2; BMI is determined by the following equation: BMI = weight/height2 (kg/m2).
• Physical condition:No significant abnormalities in medical history, including cardiovascular system, liver, kidneys, gastrointestinal system, neural system, respiratory system (eg.asthma,asthma induced by exercise,chronic obstructive pulmonary disease), mental, metabolism, etc.
• Subjects in general good health or No significant abnormalities in the opinion of the investigator as determined by vital signs and a physical examination.

You may not qualify if:

• The average daily smoking are more than 5 cigarettes within 3 months prior to screening.
• Known hypersensitivity and/or allergy to some drugs and food.
• Known history of drug or alcohol abuse.(defined as consumption of 14 units of alcohol per week:1 unit=285ml of beer; or the equivalent of 25ml of spirit, or 100ml of wine )
• Subjects who donated blood or bleeding profusely(\> 400 mL)in the 3 months preceding study screening.
• Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.
• History or presence of any disease or condition known to increase the risk of bleeding, eg.acute gastritis, duodenal ulcer, etc.
• Frequently suffers from postural hypotension.
• History of frequent nausea or vomit causes by any etiology.
• Concomitant therapy with any drugs with known hepatic enzyme-inducing or inhibiting agents that may change the activity of CYP3A4 prior to screening or during the study.
• Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal or dietary supplements within 14 days prior to screening.
• History of having any special food(including dragon fruit,mango,grapefruit,etc.),strenuous exercises,or other factors may interfere with the absorption, distribution, metabolism, or excretion of drug within 14 days prior to screening.
• Subjects with recent significant change in diet or exercise .
• Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
• Inability to consume the food provided in the study ( a high fat, high calorie meal includes two eggs for 100g, bacon 20g, a butter toast for 50g, french fries for 115g, whole milk for 240ml).This requirement only applies to subjects under fed condition.
• Presence of clinically significant abnormalities in ECG or QTc\>470ms in males,or QTc\>480ms in females.

Sponsors & Collaborators

• Guangdong Zhongsheng Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• Zhu X, Wu M, Wang H, Li H, Lin J, Peng Y, Hu Y, Li C, Ding Y. Safety, tolerability, and pharmacokinetics of the novel pan-phosphodiesterase inhibitor ZSP1601 in healthy subjects: a double-blinded, placebo-controlled first-in-human single-dose and multiple-dose escalation and food effect study. Expert Opin Investig Drugs. 2021 May;30(5):579-589. doi: 10.1080/13543784.2021.1900822. Epub 2021 Mar 25.

  PMID: 33682556 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Yanhua Ding, MD

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking for Participant, Investigator and Clinical Research Associate
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 8, 2018
• Study Start: January 5, 2018
• Primary Completion: December 21, 2018
• Study Completion: March 22, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-08

Locations

CN (1)