A Phase I Clinical Study on a New Oral Pentamidine Formulation in Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase I Clinical Study on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02210182
• Other study ID #: OCZ103-300-1401
• Status: Completed
• Phase: Phase 1
• First received: August 4, 2014
• Last updated: March 11, 2016
• Start date: August 2014
• Est. completion date: December 2015

Study information

• Verified date: March 2016
• Source: Oncozyme Pharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

Description:

This is a Phase 1, randomized, double-blind, placebo-controlled, sequential-group administration of a new oral pentamidine formulation to investigate its hepatic uptake, pharmacokinetics, safety and tolerance in subjects with hepatocellular carcinoma who undergoes thermal ablation procedure

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male or female subjects

2. 18 years of age or older

3. Radiologically established diagnosis of hepatocellular carcinoma (HCC) with tumor diameter = 5 cm

4. Suitable for and scheduled to undergo thermal ablation as treatment

5. Have a Barcelona score of 0 or A

6. Have a Child Pugh score of A or B

7. Legally and mentally able to give informed consent to participate in the study

8. Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects of the trial prior to enrolment

9. Willingness and ability to comply with scheduled visits and trial procedures

Exclusion Criteria:

1. Presence of uncontrolled diabetes, defined as glycated hemoglobin (Hb1Ac) = 8.0

2. History of clinically significant hypoglycaemia, with fasting blood glucose < 3 mmol/L within 3 months prior to signature of ICF

3. Presence of clinically significant renal impairment, defined as a creatinine clearance < 60 mL/min

4. Systolic Blood Pressure < 100 mm Hg (if deemed clinically significant by the treating physician)

5. Current or recent (< 2 years) history of pancreatitis

6. International Normalised Ratio (INR) > 1.5 or presence of severe coagulation disorders (vg but limited to prothrombin activity < 40% or a platelet count of < 40,000 / mm3)

7. Presence of known vascular invasion, bile duct invasion or extrahepatic metastasis

8. Presence of portal venous thrombosis

9. Concomitant therapy with other investigational agents or participation in another clinical trial within 3 months of signature of ICF

10. Previous use of pentamidine with treatment discontinuation of less than 6 months prior to signature of ICF

11. Any of the following conditions: Ongoing clinically significant cardiac dysrhythmias such as atrial fibrillation ; QTc interval > 450 msec for males or > 470 msec for females or uncontrolled intercurrent cardiac illness, e.g. unstable angina; severe coronary disease, ventricular arrhythmias, bradycardia < 50 bpm (unless caused by beta-blocker); a history of additional risk factors for torsades de pointes (e.g., heart failure or family history of Long QTC Syndrome)

12. Presence of clinically significant hypokalemia or hypomagnesemia

13. Concurrent use of nephrotoxic drugs

14. Concurrent use of cardiotoxic drugs

15. Concurrent use of drugs that may be associated with pancreatitis

16. History of allergy or hypersensitivity to pentamidine

17. Pregnancy or breastfeeding. All female subjects of childbearing potential must have a negative urine pregnancy test prior to first dose of study medication.

18. Acute or chronic severe medical or psychiatric condition, or laboratory abnormality that would impart, in the judgement of the investigator, excess risk associated with trial participation of study drug administration, or which in the judgement of the investigator, would make the subject inappropriate for entry into this trial

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Oral Pentamidine
Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days

Other:
• Placebo
Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days

Locations

Country	Name	City	State
Canada	Dr. Kelly Burak	Calgary	Alberta
Canada	Dr Marc Bilodeau	Montreal	Quebec
Canada	Dr Morris Sherman	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Oncozyme Pharma Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pharmacokinetics	Liver concentration of pentamidine in hepatocellular carcinoma tumor and surrounding tissue after oral administration for 3 days at different doses, measured in liver biopsies obtained during thermal ablation procedure	3 days	Yes
Secondary	plasma Pharmacokinetics	Plasma concentration of pentamidine after oral administration for 3 days at different doses	3 days	Yes
Secondary	Adverse events	Safety as assessed by adverse events (AE), vital signs and laboratory parameters	3 days	Yes
Secondary	markers of efficacy	The levels of Plasma pharmacodynamic markers of efficacy: ALT and AST	3 days	Yes
Secondary	Biomarker	Tissue biomarker of mechanism of action: Endo-exonuclease	3 days	No