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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Oral Pentamidine; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4Z6
      • Dr. Kelly Burak
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Dr Morris Sherman
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Dr Marc Bilodeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral pentamidine; Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days	Drug: Oral Pentamidine; Oral pentamidine given at 300 mg, 600 mg, 900 mg or 1200 mg QD x 3 consecutive days; Other Names: VLX103
Placebo Comparator: Placebo; Placebo 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Oncozyme Pharma Inc.
• Investigators: Study Director: Patrick Colin, B.Pharm, PhD, Verlyx Pharma Inc

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 4, 2014
• First Posted (Estimate): August 6, 2014

Study Record Updates

• Last Update Posted (Estimate): March 14, 2016
• Last Update Submitted That Met QC Criteria: March 11, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; Oral Pentamidine; Endo-exonuclease
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Pentamidine
• Other Study ID Numbers: OCZ103-300-1401