Short-term Clinical Study of CN128 in Thalassemia Patients

• Status: Completed
• Trial end date: 2019-12-17
• Target enrollment: 0
• Participant gender: All

Summary

1. Primary objectives:

• To study the tolerance and safety of multiple oral administration of CN128 in patients with thalassemia aged 16 years and above.

• To study the pharmacokinetics of CN128 in thalassemia patients aged 16 and above by multiple oral administrations of CN128

2. Design:

The study is designed as a safety, tolerability and pharmacokinetic parameters study, phase Ib trial.

The study is consisted of: multiple dose tolerance and safety study; multiple administration pharmacokinetics.

3. Subject inclusion criteria:

• Thalassemia patients with serum ferritin ≥ 500 µg/L

• Patients aged 16 and above

• HB≥80 g/L before administration

• Voluntarily participate in the experiment, and the process of obtaining informed consent met the requirements of GCP.

4. Subject exclusion criteria:

• Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive

• History of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other investigators believe that patients with potential intestinal complications

• Liver dysfunction (ALT or AST > 2.5×ULN); or renal dysfunction (serum creatinine > 1.5×ULN)

• Uncontrolled active infections

• Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs

• ect.

5. Usage:

All subjects fasted prior to administration of study drug using 240 ml warm water. The people can not drink water within 1h before administration.

6. Pharmacokinetic assessment of CN128 administration:

PK parameters of CN128 include AUC 0-t, AUC 0-∞, Cmax, Tmax, t1/2, CL/F, Vd/ F, MRT, λz, Css-av, Css-min, Css-max, Accumulation rate, Fluctuation index, etc.

7. Safety and tolerability assessments:

Evaluation was based on the incidence rate of adverse events (AE) after the administration, study termination information, vital signs, physical examination, laboratory tests and ECG.

8. Statistics

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hangzhou Zede Pharma-Tech Co., Ltd.

Criteria

Subject inclusion criteria:

• Thalassemia patients with serum ferritin ≥ 500 µg/L

• Patients aged 16 and above

• HB≥80 g/L before administration

• Voluntarily participate in the experiment, and the process of obtaining informed consent met the requirements of GCP.

Subject exclusion criteria:

• Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive

• History of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other investigators believe that patients with potential intestinal complications

• Liver dysfunction (ALT or AST > 2.5×ULN); or renal dysfunction (serum creatinine > 1.5×ULN)

• Uncontrolled active infections

• Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs

• Allergic constitution: allergic to or with contraindication of main ingredients or excipients of CN128 tablets (microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, silica, sodium stearate fumarate, Opadry)

• Patients who have abnormal ECG with clinical significance: congenital long QT syndrome or known family history of long QT syndrome; QTc > 450ms (male) or QTc > 470ms (female); patients who have ventricular or atrial tachyarrhythmia with clinical significance, etc

• Family planning participants (including male subjects) during or within three months after the trial

• Patients with a history of blood donation within 3 months before the trial

• Patients with a history of smoking (more than 5 cigarettes or products with equivalent nicotine per day), alcoholism (more than 14 units of alcohol per week: 1 alcohol unit equals 10 mL or 8 g pure alcohol; 25 mL 40% liquor, 330 mL 5% beer, 175 mL 12% red wine equals 1.0, 1.5, 2.0 alcohol units respectively), drug abuse and addiction history

• Patients who smoke, drink or eat any food containing alcohol, xanthine or grapefruit (including chocolate, tea, coffee or cola drinks) within 48 h before using of test drug

• The subjects should not join in other clinical drug or instrument study or some other clinical studies within 3 months before taking the study drug, except for non interventional studies;

• Patients with positive results of nicotine and urine drug screening

• Patients with difficulty in venous blood collection

• Patients with positive blood pregnancy test results

• Any patient with conditions which the investigators resume inappropriate to participate in this study, such as: poor health status, poor compliance, unwillingness or inability to comply with treatment regimens, including delayed visits