Istaroxime Infusion for 24 Hours in Chinese Healthy Volunteers

Phase 1

• Conditions: Healthy
• Interventions: Drug: istaroxime; Drug: 9% Saline (NS)

• Registration Number: NCT02477449
• Lead Sponsor: Lee's Pharmaceutical Limited

Brief Summary

Phase 1 study to investigate safety of istaroxime in healthy chinese volunteers.

Detailed Description

32 subjects (F: M=1:1) were randomized in three dose groups (0.25-0.5-1.0ug/kg/min). 8 subjects in 0.25ug/kg/min group were administrated Istaroxime + 0.9% NS; 12 subjects in 0.5ug/kg/min or 1.0 ug/kg/min group randomly received Istaroxime placebo + 0.9% NS (2 subjects), 0.9% NS alone (2 subjects) and Istaroxime + 0.9% NS (8 subjects). All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic. At least 1 week should be kept between two dose groups. Escalation to the higher dose will occur after the lower dose group has been completed and no significant safety issues are found.

Study Timeline

• Study Start: 2015-05
• Status Verified: 2015-06
• Study First Submitted: 2015-06-17
• Study First Submitted QC: 2015-06-19
• Last Update Submitted: 2015-06-19
• Study First Posted: 2015-06-22
• Last Update Posted: 2015-06-22
• Primary Completion: 2015-07
• Study Completion: 2015-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Age at 18-45 years (inclusive)
2. Male or Non-pregnant, non-lactating women
3. Chinese healthy subjects
4. Body mass index (BMI) at 19-24 kg/m2 (inclusive) and body weight at 50-100kg
5. Lab examinations (include but not limited: Hemoglobin, white blood cell counting, differential count, creatinine,Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT),Total bilirubin and urinalysis) are within normal range or out of normal range but no clinical significance.
6. Vital signs in screening phase: SBP100-139mmHg, DBP 50-89 mmHg, pulse rate 45-90 bpm. Holter is within normal range or out of normal range but no clinical significance.
7. Both physical examination and ECG at baseline are normal or abnormal but no clinical significance
8. Women of childbearing age during the trial must be willing to use a medically acceptable method of contraception, which include surgical sterilization (tubal ligation / hysterectomy), and double barrier methods of hormonal contraception.
9. Subjects well communicate with investigators, understanding the requirements of investigators and being willing to sign the ICF before conducting any study-related procedure.
10. Subjects are willing to stay at the phase I ward throughout the study.

Exclusion Criteria

1. Disease history in liver, kidney, endocrine, cardiovascular, neurological, psychiatric, gastrointestinal tract, lungs, immune, skin, blood, or metabolic disorders or cancer, that may have great impact on the study results.
2. Presence of pancreatitis, intestinal obstruction, glaucoma, prostatic hypertrophy, adrenal disease, hyperthyroidism or gallbladder disease (subjects had experienced cholecystectomy will not be excluded)
3. History of clinical significant disease in the past 4 weeks before screening visit
4. Presence of diseases which are known to disturb the absorption, distribution, metabolism or excretion of Istaroxime
5. Physical examinations, medical history, ECG, vital signs or lab examination are deemed to be abnormal and clinical significant
6. Be intolerant or allergy to Istaroxime, lactose or any similar substances
7. Significantly abnormal diets are conducted within 4 weeks before screening visit
8. Blood donation or loss equal to or exceeds 400ml in the past 6 months
9. Participating in the any other drug study in the past 3 months
10. Administrated OTC drugs including vitamin supplements and herbal (Occasional use of paracetamol will not be excluded)
11. Regular use of any prescription drug (Hormonal birth control pills or hormone replacement therapy will not be excluded)
12. Drinking beverage or eat food containing caffeinated / xanthine or poppy seed since 48 hours before study drugs administration; or drinking beverage or eat food containing grapefruit, oranges or Chinese tea 14 days before the study drug administration
13. Receiving the therapy of drugs including cytochrome P450 3A4 or cytochrome P450 2C8 inhibitors or inducers (eg barbiturates, carbamazepine, erythromycin, phenytoin, thiazoline TZDs, Rifampin)
14. Women at Lactation period or with positive pregnancy test
15. Tongue piercing or lip piercing occurred 30 days before the study drug administration
16. Smoke or tobacco is used 60 days before the study drug administration
17. History of abusing any substance including infusion drugs, alcohol and opium
18. Positive alcohol breathing test within 1day or drink alcohol within 1week
19. Abusing drugs (include Opioids, oxycodone, methamphetamine, amphetamine, cannabinoids, cocaine, barbiturates, benzodiazepines class, methadone, buprenorphine and phencyclidine)
20. History of heart disease
21. Planning to be pregnant in the recent 3 months
22. Participating any other interventional strudy in the past 30 days
23. History of bronchial asthma or blood porphyria disease
24. HbsAg, anti-HCV, anti-HIV or anti - syphilis are positive
25. Holter examination is abnormal and clinical significant
26. Subjects are not eligible for the study judged by investigators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mid dose group	9% Saline (NS)	12 subjects in 0.5ug/kg/min group randomly received Istaroxime placebo + 0.9% NS (2 subjects), 0.9% NS alone (2 subjects) and Istaroxime + 0.9% NS (8 subjects). All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic.
high dose group	9% Saline (NS)	12 subjects in 1.0 ug/kg/min group randomly received Istaroxime placebo + 0.9% NS (2 subjects), 0.9% NS alone (2 subjects) and Istaroxime + 0.9% NS (8 subjects). All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic.
high dose group	istaroxime	12 subjects in 1.0 ug/kg/min group randomly received Istaroxime placebo + 0.9% NS (2 subjects), 0.9% NS alone (2 subjects) and Istaroxime + 0.9% NS (8 subjects). All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic.
low dose group	istaroxime	8 subjects in 0.25ug/kg/min group were administrated Istaroxime + 0.9% NS; All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic.
mid dose group	istaroxime	12 subjects in 0.5ug/kg/min group randomly received Istaroxime placebo + 0.9% NS (2 subjects), 0.9% NS alone (2 subjects) and Istaroxime + 0.9% NS (8 subjects). All the subjects were given infusion of study drugs for 24 hours, and then were observed for 48 hours in the clinic.

Primary Outcome Measures

Name	Time	Method
safety of istaroxime in healthy volunteers is measured by varition of heart functon, blood pressure and heart ratio	one week	safety of istaroxime in healthy volunteers is measured by

Trial Locations

Locations (1)

The 307th hospital of chinese People's liberation army; 🇨🇳 Beijing, China