Multiple Ascending Dose Study of CG200745 'Ivaltinostat' Oral Capsule

A Phase I, Double Blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Orally Administered 'Ivaltinostat' Capsule in Healthy Male Volunteers

A Phase I, Double blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Orally Administered 'CG-745' Capsule in Healthy Male Volunteers

Study Overview

• Status: Active, not recruiting
• Conditions: Fibrosis; Solid Tumor; Hematologic Malignancy
• Intervention / Treatment: Other: Placebo; Drug: Ivaltinostat

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. Patients who are between 19 to 50 years of age at screening visit.

2. Patients who have body weight between 50.0 to 90.0 kg, and Body Mass Index (BMI) of 18.0 to 30.0 kg/m2 at screening visit.

   ☞ BMI (kg/m2) = Body Weight (kg) / {Height(m)}2

3. Patients who have signed informed consent prior to study participation after receiving detailed information on the purpose and details of the study, the characteristics of the test drug, and the expected adverse events.
4. Patients who are determined to be eligible by the investigator after evaluation of the following screening results: study questionnaires, physical examination, laboratory test, electrocardiogram, vital signs).

Exclusion Criteria

1. Medical history of clinically significant hepatic, renal, neurological, respiratory, endocrine, hematological, oncological, cardiovascular, urinary, and/or psychiatric disorder.
2. History of gastrointestinal disease or gastrointestinal surgery (except for simple appendectomy or hernia operation) that may affect the pharmacokinetic and/or safety evaluation of IP medications.
3. Known clinically significant hypersensitivity to HDAC inhibitors and/or other drugs.
4. Systolic blood pressure (SBP) less than 90 mmHg or over 140 mmHg; diastolic blood pressure (DBP) less than 50 mmHg or over 95 mmHg; pulse rate less than 45/min or over 100/min in the sitting position after a 5-minute rest.

5. Patients who show one or more of the following findings during screening (including additional tests):

   • AST (GOT) or ALT (GPT) exceeds 1.5 times the upper limit of the normal range ② Total bilirubin exceeds 1.5 times the upper limit of the normal range ③ Absolute neutrophil count (ANC) lower than 2,000/uL ④ Hb less than 12.5 g/dL ⑤ Platelets count less than 130,000/uL
6. Participation in another clinical study or bioequivalence study within 180 days prior to the first IP administration.
7. Positive result in serum tests (hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis).
8. Donation of whole blood within 60 days, apheresis within 30 days, or transfusion within 30 days prior to the first IP administration.
9. Exposure to prescribed medications or herbal medicines 2 weeks prior to the first IP administration, or any general medication (OTC drug), health supplements, and/or vitamin supplements within 1 week prior to the first investigational product administration (the subject may still participate if the principal investigator determines that the subject is eligible for enrollment).
10. History of heavy smoking (more than 10 cigarettes/day) within three months prior to the first IP administration, or positive test result in urine cotinine test.
11. Excessive caffeine intake (> 5 units/day, 1 unit = 100 mg), excessive alcohol intake (> 21 units/week, 1 unit = 10 g of pure alcohol), or inability to abstain from drinking during admission period.

12. Inability to use a medically acceptable contraceptive method* for the duration of the study and up to 3 months after the last IP administration.

    * Medically acceptable contraception:

    • Use of intrauterine device (by spouse or partner) with a proven pregnancy prevention rate.
    • Concomitant use of barrier method (male or female) and spermicide.
    • Patient's or partner's surgery (vasectomy, salpingectomy, tubal ligation, or hysterectomy).
13. Patients who are determined to be ineligible to participate in the study by the principal investigator due to other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo capsule
Experimental: Cohort 1 - 4; Cohort 1 : 50 mg/day Cohort 2 : 100 mg/day Cohort 3: 200mg/day [Cohort 4: 300mg/day: based on the result of Safety Review Meeting (SRM)]	Drug: Ivaltinostat; Ivaltinostat capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma Pharmacokinetic measures (Cmax, Cmax-ss)	up to 4 weeks
Plasma Pharmacokinetic measures (AUC max, AUCmax-ss)	up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The Number of Participants Who Experienced Serious or Non-Serious Adverse Events	Up to 4 weeks for each dosing cohort

Collaborators and Investigators

• Sponsor: Machaon Biotherapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: CG200745-1-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No