NCT03935633

Brief Summary

  • 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
  • Design:
  • 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
  • ect.
  • Usage:
  • Pharmacokinetic assessment of CN128 administration:
  • Safety and tolerability assessments:
  • Statistics

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 3, 2018

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

April 18, 2019

Completed
14 days until next milestone

First Posted

Study publicly available on registry

May 2, 2019

Completed
4 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 6, 2019

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 17, 2019

Completed
Last Updated

June 9, 2023

Status Verified

December 1, 2019

Enrollment Period

5 months

First QC Date

April 18, 2019

Last Update Submit

June 8, 2023

Conditions

Thalassemia

Outcome Measures

Primary Outcomes (31)

  • Height (Unit: m)

    The patient's height will be determined, and it's one kind of Physical examination.

    Day 11

  • Weight (Unit: kg)

    The patient's weight will be determined, and it's one kind of Physical examination.

    Day 11

  • Generally Phisical examination

    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.

    Day 11

  • Pulse (Unit: bpm)

    The patient's pulse will be determined, and it's one kind of vital signs checks.

    Day 1 to Day 11

  • Respiration (Unit: bpm)

    The patient's respiration will be determined, and it's one kind of vital signs checks.

    Day 1 to Day 11

  • Blood pressure (Unit: mmHg)

    Both patient's systolic and diastolic blood pressure will be measured, and it's one kind of vital signs checks.

    Day 1 to Day 11

  • Temperature (Unit: ℃)

    The patient's temperature will be determined, and it's one kind of vital signs checks.

    Day 1 to Day 11

  • Electrocardiogram: P-R (Unit: ms), QRS (Unit: ms), QTc (Unit: ms), etc

    The patient's electrocardiogram will be measured, and it's one kind of laboratory test.

    Day 1 to Day 11

  • WBC (Unit: 10E9/L), RBC (Unit: 10E9/L), NEUT (Unit: 10E9/L), BASO (Unit: 10E9/L)

    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.

    Day 3, Day 7, Day 11

  • ALT (Unit: U/L), AST (Unit: U/L)

    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.

    Day 3, Day 7, Day 11

  • Fibrinogen (Unit: g/L), Prothrombin time (Unit: s), APTT (Unit: s)

    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.

    Day 11

  • Serum iron (Unit: umol/L)

    The patient's serum iron will be determined at Day 11, and it's one kind of laboratory test.

    Day 11

  • Urine colour

    The colour of urine will be observed at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.

    Day 3, Day 7, Day 11

  • Urine appearance

    The appearance of urine will be observed at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.

    Day 3, Day 7, Day 11

  • Urine glucose (Unit: mmol/L)

    The glucose of urine will be determined at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.

    Day 3, Day 7, Day 11

  • Urine protein (Unit: g/L)

    The protein of urine will be determined at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.

    Day 3, Day 7, Day 11

  • Number of subjects with adverse events

    It's the number of subjects with adverse events after administration.

    Day 1 to Day 11

  • AUC0-t of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • AUC0-∞ of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Cmax of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Tmax of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • t1/2 of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • CL/F of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Vd/F of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • MRT of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Css-av of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Css-min of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Css-max of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Accumulation rate of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • Fluctuation index of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

  • λz of CN128

    Pharmacokinetics parameters

    Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11

Study Arms (2)

First Dosage

EXPERIMENTAL

The dose of CN128 is 20 mg/kg bw， bid.

Drug: CN128 Tablets

Second Dosage

EXPERIMENTAL

The dose of CN128 is 15 mg/kg bw， bid.

Drug: CN128 Tablets

Interventions

CN128 TabletsDRUG

Iron chelator， oral tablets

First DosageSecond Dosage

Eligibility Criteria

Age16 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The first affiliated hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 18, 2019

First Posted

May 2, 2019

Study Start

December 3, 2018

Primary Completion

May 6, 2019

Study Completion

December 17, 2019

Last Updated

June 9, 2023

Record last verified: 2019-12

Locations

CN(1)