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

NCT02210182 | Completed Phase 1 DMC

• 1 other identifier: OCZ103-300-1401
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

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

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Oral Pentamidine; Endo-exonuclease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• plasma Pharmacokinetics

  3 days

• Adverse events

  3 days

• markers of efficacy

  3 days

• Biomarker

  3 days

Study Arms (2)

Oral pentamidine

EXPERIMENTAL

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

Drug: Oral Pentamidine

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Oral Pentamidine DRUG

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

Also known as: VLX103

Oral pentamidine

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects
• years of age or older
• Radiologically established diagnosis of hepatocellular carcinoma (HCC) with tumor diameter ≤ 5 cm
• Suitable for and scheduled to undergo thermal ablation as treatment
• Have a Barcelona score of 0 or A
• Have a Child Pugh score of A or B
• Legally and mentally able to give informed consent to participate in the study
• 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
• Willingness and ability to comply with scheduled visits and trial procedures

You may not qualify if:

• Presence of uncontrolled diabetes, defined as glycated hemoglobin (Hb1Ac) ≥ 8.0
• History of clinically significant hypoglycaemia, with fasting blood glucose \< 3 mmol/L within 3 months prior to signature of ICF
• Presence of clinically significant renal impairment, defined as a creatinine clearance \< 60 mL/min
• Systolic Blood Pressure \< 100 mm Hg (if deemed clinically significant by the treating physician)
• Current or recent (\< 2 years) history of pancreatitis
• 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)
• Presence of known vascular invasion, bile duct invasion or extrahepatic metastasis
• Presence of portal venous thrombosis
• Concomitant therapy with other investigational agents or participation in another clinical trial within 3 months of signature of ICF
• Previous use of pentamidine with treatment discontinuation of less than 6 months prior to signature of ICF
• 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)
• Presence of clinically significant hypokalemia or hypomagnesemia
• Concurrent use of nephrotoxic drugs
• Concurrent use of cardiotoxic drugs
• Concurrent use of drugs that may be associated with pancreatitis

Sponsors & Collaborators

• Oncozyme Pharma Inc.: lead

Study Sites (3)

Dr. Kelly Burak

Calgary, Alberta, T2N4Z6, Canada

Location

Dr Morris Sherman

Toronto, Ontario, M5G 2N2, Canada

Location

Dr Marc Bilodeau

Montreal, Quebec, H2X 3J4, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Pentamidine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Benzamidines; Amidines; Organic Chemicals

Study Officials

• Patrick Colin, B.Pharm, PhD

  Verlyx Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2014
• First Posted: August 6, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 14, 2016

Record last verified: 2016-03

Locations

CA (3)