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Short-term Clinical Study of CN128 in Thalassemia Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03935633
Recruitment Status : Completed
First Posted : May 2, 2019
Last Update Posted : December 19, 2019
Sponsor:
Information provided by (Responsible Party):
Hangzhou Zede Pharma-Tech Co., Ltd.

Brief 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

Condition or disease Intervention/treatment Phase
Thalassemia Drug: CN128 Tablets Phase 1

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Clinical Study to Assess the Safety, Tolerability and Pharmacokinetic Parameters of CN128 Tablets to Administration in Thalassemia Patients Aged 16 and Above
Actual Study Start Date : December 3, 2018
Actual Primary Completion Date : May 6, 2019
Actual Study Completion Date : December 17, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arm Intervention/treatment
Experimental: First Dosage
The dose of CN128 is 20 mg/kg bw, bid.
Drug: CN128 Tablets
Iron chelator, oral tablets

Experimental: Second Dosage
The dose of CN128 is 15 mg/kg bw, bid.
Drug: CN128 Tablets
Iron chelator, oral tablets




Primary Outcome Measures :
  1. Height (Unit: m) [ Time Frame: Day 11 ]
    The patient's height will be determined, and it's one kind of Physical examination.

  2. Weight (Unit: kg) [ Time Frame: Day 11 ]
    The patient's weight will be determined, and it's one kind of Physical examination.

  3. Generally Phisical examination [ Time Frame: Day 11 ]
    The patient's skin, neck, eyes, ears, nose, throat, chest, back, lymph nodes, arms, legs, nervous system, etc. will be observed, and it's one kind of Physical examination.

  4. Pulse (Unit: bpm) [ Time Frame: Day 1 to Day 11 ]
    The patient's pulse will be determined, and it's one kind of vital signs checks.

  5. Respiration (Unit: bpm) [ Time Frame: Day 1 to Day 11 ]
    The patient's respiration will be determined, and it's one kind of vital signs checks.

  6. Blood pressure (Unit: mmHg) [ Time Frame: Day 1 to Day 11 ]
    Both patient's systolic and diastolic blood pressure will be measured, and it's one kind of vital signs checks.

  7. Temperature (Unit: ℃) [ Time Frame: Day 1 to Day 11 ]
    The patient's temperature will be determined, and it's one kind of vital signs checks.

  8. Electrocardiogram: P-R (Unit: ms), QRS (Unit: ms), QTc (Unit: ms), etc [ Time Frame: Day 1 to Day 11 ]
    The patient's electrocardiogram will be measured, and it's one kind of laboratory test.

  9. WBC (Unit: 10E9/L), RBC (Unit: 10E9/L), NEUT (Unit: 10E9/L), BASO (Unit: 10E9/L) [ Time Frame: Day 3, Day 7, Day 11 ]
    The patient's blood examination(WBC (Unit: 10E9/L), RBC (Unit: 10E9/L), NEUT (Unit: 10E9/L), BASO (Unit: 10E9/L), etc.)will be determined at Day 3, Day 7, Day 11 respectively, and it's one kind of laboratory test.

  10. ALT (Unit: U/L), AST (Unit: U/L) [ Time Frame: Day 3, Day 7, Day 11 ]
    The patient's blood biochemical examination(ALT (Unit: U/L), AST (Unit: U/L), etc.)will be determined at Day 3, Day 7, Day 11 respectively,and it's one kind of laboratory test.

  11. Fibrinogen (Unit: g/L), Prothrombin time (Unit: s), APTT (Unit: s) [ Time Frame: Day 11 ]
    The patient's blood coagulation function ( fibrinogen (Unit: g/L), prothrombin time (Unit: s), APTT (Unit: s) , etc.) will be determined at Day 11, and it's one kind of laboratory test.

  12. Serum iron (Unit: umol/L) [ Time Frame: Day 11 ]
    The patient's serum iron will be determined at Day 11, and it's one kind of laboratory test.

  13. Urine colour [ Time Frame: Day 3, Day 7, Day 11 ]
    The colour of urine will be observed at Day 3, Day 7, Day 11 respectively,and it's one kind of laboratory test.

  14. Urine appearance [ Time Frame: Day 3, Day 7, Day 11 ]
    The appearance of urine will be observed at Day 3, Day 7, Day 11 respectively,and it's one kind of laboratory test.

  15. Urine glucose (Unit: mmol/L) [ Time Frame: Day 3, Day 7, Day 11 ]
    The glucose of urine will be determined at Day 3, Day 7, Day 11 respectively,and it's one kind of laboratory test.

  16. Urine protein (Unit: g/L) [ Time Frame: Day 3, Day 7, Day 11 ]
    The protein of urine will be determined at Day 3, Day 7, Day 11 respectively,and it's one kind of laboratory test.

  17. Number of subjects with adverse events [ Time Frame: Day 1 to Day 11 ]
    It's the number of subjects with adverse events after administration.

  18. AUC0-t of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  19. AUC0-∞ of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  20. Cmax of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  21. Tmax of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  22. t1/2 of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  23. CL/F of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  24. Vd/F of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  25. MRT of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  26. Css-av of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  27. Css-min of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  28. Css-max of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  29. Accumulation rate of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  30. Fluctuation index of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters

  31. λz of CN128 [ Time Frame: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 ]
    Pharmacokinetics parameters



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03935633


Locations
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China, Zhejiang
The first affiliated hospital, Zhejiang University
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
Hangzhou Zede Pharma-Tech Co., Ltd.

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Responsible Party: Hangzhou Zede Pharma-Tech Co., Ltd.
ClinicalTrials.gov Identifier: NCT03935633    
Other Study ID Numbers: D160605-2
First Posted: May 2, 2019    Key Record Dates
Last Update Posted: December 19, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn