A Phase I Study of SHR1459 in Healthy Subjects

NCT04455100 | Completed Phase 1

• 1 other identifier: SHR1459-I-106
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period. Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7 following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole 200 mg with 240 mL of ambient temperature water.

Conditions

Health, Subjective

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics parameter: Cmax of SHR1459

  Peak Plasma Concentration (Cmax) of SHR1459

  from Day 1 to Day 9

• Pharmacokinetics parameter: AUC of SHR1459

  Area under the plasma concentration versus time curve (AUC) of SHR1459

  from Day 1 to Day 9

Secondary Outcomes (4)

• Pharmacokinetics parameter: Tmax of SHR1459

  from Day 1 to Day 9

• Pharmacokinetics parameter: T1/2 of SHR1459

  from Day 1 to Day 9

• Pharmacokinetics parameter: CL/F of SHR1459

  from Day 1 to Day 9

• Pharmacokinetics parameter: Vz/F of SHR1459

  from Day 1 to Day 9

Study Arms (1)

SHR1459

EXPERIMENTAL

Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period. Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7 following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole 200 mg with 240 mL of ambient temperature water.

Drug: SHR1459/Itraconazole

Interventions

SHR1459/Itraconazole DRUG

SHR1459 will be administered on Day 1 and Day 7. Itraconazole will be administered on Day 4 to Day 8

SHR1459

Eligibility Criteria

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

You may qualify if:

• Sign the informed consent before the trial and fully understand the content, process and possible adverse of the trial;
• Able and willing to complete research according to the requirements of the trial;
• Age at the date of signing informed consent 18 to 55 years old (inclusive), male and female;
• Male body weight ≥50 kg, female body weight ≥45 kg, body mass index (BMI) between ≥18.0 and ≤26.0 kg/m2, inclusive;
• Health status: lack of medical history of heart, liver, kidney, digestive tract, nervous system, mental disorders and metabolic abnormalities;
• Comprehensive physical examination (vital signs, physical examination), routine laboratory examination (blood routine, blood biochemistry, urine routine, etc.), X-chest radiograph, abdominal ultrasound (liver, gallbladder, bile duct, spleen, pancreas, kidney), etc, normal or abnormal and no clinical significance;
• lead ECG is normal, QTcF for men \<430 ms, QTcF for women \<450 ms, and heart rate \>60;
• Creatinine clearance (CLCr) ≥80 mL/min, and creatinine is less than or equal to the upper limit of normal value;
• A negative pregnancy test for females of childbearing potential;
• Consent to abstinence or use of effective nondrug contraception during the study period and for at least 3 months after the last study drug administration (for women, abstinence or use of effective nondrug contraception during the two weeks prior to study entry is also required).

You may not qualify if:

• Blood donation or loss of more than 200 mL of blood within 1 month of screening; or blood donation or loss of more than 400 mL of blood within 3 months of screening; or received blood
• Allergic constitution, including severe drug allergy or history of drug allergy; history of allergy to SHR1459, itraconazole, or its accessories;
• Subject has a history of drug abuse in past 5 years or drug abuse in past 3 months, or is positive for drugs of abuse (eg, morphine/methamphetamine/ketamine/ tetrahydrocannabinolic acid /methylenedioxyethylamphetamine );
• History of regular alcohol and smoke consumption( exceeding or equal an average weekly intake of 14 standard drinks; 1 drink=150 mL of wine or 360 mL of beer or 45 mL of hard liquor; smoke more than or equal to 5 cigarettes per day)or will not refrain from smoking and drinking during the study;
• History of cardiovascular dysfunction, myocarditis, coronary heart disease, pathological arrhythmia, stroke and other cardiovascular diseases;
• Lung diseases, including invasive lung disease, pneumonia, dyspnea, etc;
• History of chronic kidney disease, renal insufficiency, renal anemia;
• History of dysphagia or any gastrointestinal disease that affects drug absorption;
• Any uncontrolled peptic ulcer, colitis, pancreatitis, etc;
• Had a surgery within 6 months of screening;
• Important organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and skeletal muscle system (such as uncontrolled diabetes, hypertension, etc.), in the investigator's judgment it is not suitable to participate in this trial;
• Have taken hepatotoxic drugs for a long period of time (more than 2 consecutive weeks) (such as acetaminophen, statin lipid-lowering drugs, azithromycin, dapsone, clarithromycin, fluconazole, ketoconazole) before the screening;
• Participated in other clinical trials or used drugs related to this trial within 3 months before screening;
• Have taken any drugs that alter the activity of liver enzymes 28 days before or during the study;
• Have taken any prescription or over-the-counter medicine 14 days before study drug administration;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: collaborator

Study Sites (1)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2020
• First Posted: July 2, 2020
• Study Start: July 17, 2020
• Primary Completion: August 14, 2020
• Study Completion: August 14, 2020
• Last Updated: October 18, 2021

Record last verified: 2021-10

Locations

CN (1)