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

Phase 1

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Other: Placebo; Drug: Oral Pentamidine

• Registration Number: NCT02210182
• Lead Sponsor: Oncozyme Pharma Inc.

Brief 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

Detailed 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

Study Timeline

• Study Start: 2014-08
• Study First Submitted: 2014-08-04
• Study First Submitted QC: 2014-08-04
• Study First Posted: 2014-08-06
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-11
• Last Update Posted: 2016-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days
Oral pentamidine	Oral Pentamidine	Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days

Primary Outcome Measures

Name	Time	Method
pharmacokinetics	3 days	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

Secondary Outcome Measures

Name	Time	Method
plasma Pharmacokinetics	3 days	Plasma concentration of pentamidine after oral administration for 3 days at different doses
markers of efficacy	3 days	The levels of Plasma pharmacodynamic markers of efficacy: ALT and AST
Biomarker	3 days	Tissue biomarker of mechanism of action: Endo-exonuclease
Adverse events	3 days	Safety as assessed by adverse events (AE), vital signs and laboratory parameters

Trial Locations

Locations (3)

Dr. Kelly Burak; 🇨🇦 Calgary, Alberta, Canada

Dr Morris Sherman; 🇨🇦 Toronto, Ontario, Canada

Dr Marc Bilodeau; 🇨🇦 Montreal, Quebec, Canada