Clinical trial NCT04333134: A Trial of SHR3162 in Healthy Caucasian Volunteers
Official title: A Phase 1, Open-Label, Two-Center Study to Evaluate the Safety and Pharmacokinetics of Single-Dose Fluzoparib in Healthy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Atridia Pty Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study will enroll a single cohort of healthy Caucasian subjects with an approximately one-to-one ratio of male to female subjects
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and PK characteristics of a single oral dose of fluzoparib in healthy Caucasian and Chinese subjects


Eligibility criteria: Inclusion Criteria:

1. Healthy Caucasian subjects, male and female, 18 to 45 years of age, inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests;
2. Male body weight ≥50 kg, female body weight ≥45 kg, body mass index (BMI) between ≥18.0 and ≤29.0 kg/m2, inclusive;
3. Female subjects agree not to be pregnant or lactating from beginning of the study screening to 90 days after trial completion:

   * A negative blood and urine pregnancy test for females of childbearing potential at Screening and at Check-in, respectively;
   * Females of reproductive potential are willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy; A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year), when used consistently and correctly. Females of non-childbearing potential will not be required to use contraception. Females of non-child bearing potential are defined as permanently sterile (eg, due to hysterectomy) or postmenopausal (defined as at least 12 months following cessation of menses without an alternative medical cause and serum FSH levels \>25 IU/L).
4. Males agree to refrain from donating sperm and fathering a child during the study and for at least 90 days after fluzoparib administration; male participants must agree to remain abstinent or must ensure a condom is used for all sexual activity (with a male or female partner) for this same duration.
5. Able and willing to refrain from caffeine or caffeine-containing products, alcohol, fruit juices, and smoking/tobacco products from at least 48 hours prior to Check-In until the end of Safety Follow Up;
6. Able and willing to refrain from eating and drinking poppy seed-containing products and grapefruit-related citrus fruits (eg, Seville oranges, pomelos) within 7 days prior to dosing until after collection of the final PK blood sample (Day 4);
7. Able and willing to refrain from strenuous exercise (heavy lifting, weight training, calisthenics, aerobics) within 7 days prior to dosing until after collection of the final PK blood sample (Day 4);
8. Willing and able to comply with all scheduled visits, study procedures, and provides written informed consent.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neuropsychiatric disease, or any condition that may affect drug absorption, distribution, metabolism, and excretion;
2. Had a severe infection, trauma or major surgery within 4 weeks of screening and at Check-In; plan to have a surgery during the trial;
3. A past medical history of ECG abnormalities, documented cardiac arrhythmias, or cardiovascular disease; or QTcF interval \>450 msec for males, \>470 msec for females, or \<300 msec;
4. Subject's systolic blood pressure (SBP) is \>140 or \<90 mmHg, diastolic blood pressure (DBP) is \>90 or \<50 mmHg, resting heart rate \<40 or \>100 bpm, and respiratory rate \<10 or \>20 breaths/min at Screening or Check-in after resting in a semi-supine position for 5 minutes. Vitals can be repeated twice (a minimum of 1 to 2 minutes apart) based on the investigator's judgment;
5. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or any active systemic viral infection requiring therapy (eg, hepatitis B or C);
6. Subject has a history of type 1 hypersensitivity to any medication;
7. Subject has evidence of substance abuse, a history of substance abuse, or is positive for drugs of abuse (eg, methamphetamines, opiates, methadone, cocaine, amphetamines, cannabinoids, tricyclic antidepressants, phencyclidine, barbiturates, benzodiazepines), or alcohol at Screening and Check-in (Day -1);
8. History of symptomatic hypoglycemia;
9. Subjects who smoke more than 5 cigarettes per day or will not refrain from smoking starting from at least 48 hours prior to screening and check-in on Day -1, and during the study;
10. History of regular alcohol consumption in the past 3 months exceeding an average weekly intake of 14 standard drinks; 1 drink=5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor;
11. Subject has used prescription medications within 14 days or, as per PI discretion, over-the-counter medications, dietary/nutritional supplements (except hormonal contraceptives, paracetamol under 2 grams/day, vitamin supplements) within 7 days or 5 half-lives prior to fluzoparib administration;
12. Treatment with an investigational drug within 3 months (or 5 half-lives, whichever is longer) of dosing;
13. Use of medications affecting liver metabolism within 1 month of screening;
14. 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 within 8 weeks of screening;
15. Any other major illness/condition that, in the investigator's judgment, substantially increased the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response.

Primary outcomes:
measure: Pharmacokinetic - Cmax
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
measure: Pharmacokinetic - AUC∞
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
measure: Pharmacokinetic - Tmax
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
measure: Pharmacokinetic - CL/F
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
measure: Pharmacokinetic - Vz/F
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
measure: Pharmacokinetic - t1/2
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 10, 24, 48, and 72 hr post-dose
Secondary outcomes:
measure: Adverse events
timeFrame: Screening up to study completion, approximately 5 weeks
measure: Laboratory results
timeFrame: Screening up to study completion, approximately 5 weeks
measure: Vital signs
timeFrame: Screening up to study completion, approximately 5 weeks
measure: Electrocardiogram
timeFrame: Screening up to study completion, approximately 5 weeks
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Atridia Pty Limited
state: New South Wales
Study officials:
References: