Study to Evaluate the PK of Single and Optional Multiple Dosing Regimens of MR Formulations of PCS499 Compared to Trental® Administered to Healthy Subjects

A Phase I, Single Centre, Open-Label, Non-Randomised Study to Evaluate the PK of Single and Optional Multiple Dosing Regimens of MR Formulations of PCS499 Compared to Trental® (Pentoxifylline) Administered to Healthy Subjects Under Fed Conditions

This was a Phase I, single centre, open-label, non-randomised study and was designed to be conducted in up to 2 parts. The purpose of Part 1 was to identify a MR formulation of PCS499 that would provide an optimal dosing regimen in patients. The purpose of Part 2 of the study was to generate repeat dose information for the selected MR formulation of PCS499 in order to provide additional PK information for future patient studies.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PCS499; Drug: Trental

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female subjects
2. Aged 18 to 55 years, inclusive
3. Subjects who were healthy as determined by no clinically relevant abnormalities identified by a detailed medical history, full physical examination, vital signs, 12-lead resting electrocardiogram (ECG; corrected QT interval [QTc] ≤450, QRS <120, PR <220; normal morphology) performed at the screening visit and prior to each dosing
4. Body mass index (BMI) of 18.0 to 35.0 kg/m2 inclusive or, if outside the range, considered not clinically significant by the investigator and body weight >50 kg
5. Subjects who were willing and able to be confined at the clinical research centre for the scheduled inpatient visits
6. Ability to swallow multiple tablets whole

Exclusion Criteria:

1. Subject had a clinically significant history of GI, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, and/or lipid metabolism disorders and/or drug hypersensitivity
2. Subject had a known or suspected malignancy with the exception of basal cell carcinoma
3. Subject had a positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCV Ab) at the screening visit
4. Female subjects who were pregnant or lactating (all female subjects required a negative serum pregnancy test at the screening and a negative urine pregnancy test at each admission).
5. Subject had active disease or symptoms within 7 days prior to Day -1, such as nausea, vomiting, diarrhoea, and infection
6. Subject had undergone a hospital admission or major surgery within 30 days prior to the Screening visit
7. Subjects who had taken part in Part 1 were not permitted to take part in Part 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCS499 MR Tablet Prototype 2; 600 mg single dose	Drug: PCS499; MR tablet
Active Comparator: Trental MR tablet 400mg; single dose	Drug: Trental; comparator tablet
Experimental: PCS499 MR Tablet Prototype 4; 600mg single dose	Drug: PCS499; MR tablet
Experimental: PCS499 MR Tablet Prototype 1; 600mg single dose	Drug: PCS499; MR tablet
Active Comparator: Trental MR Tablet; 400 mg multiple dose	Drug: Trental; comparator tablet
Experimental: PCS499 MR Tablet 900mg; multiple dose	Drug: PCS499; MR tablet
Experimental: PCS499 MR Tablet 600mg; multiple dose	Drug: PCS499; MR tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentrations (Cmax) for Part 1	Serial blood sampling at specified time points for determination of plasma concentration-time profiles	Blood samples will be drawn prior to single dose administration of study drug and at 11 other timepoints in a 24 hour period.
Maximum plasma concentrations (Cmax) in Part 2	Serial blood sampling at specified time points for determination of plasma concentration-time profiles	Blood sampling will be drawn prior to the single dose administration on Days 1 & 4 and at 11 other timepoints in the following 24 hours. In addition, pre-dose trough samples will be taken on Days 2 &3.

Collaborators and Investigators

• Sponsor: Processa Pharmaceuticals
• Collaborators: Quotient Sciences
• Investigators: Principal Investigator: Sharan Sidhu, MBChB, Quotient Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2018
• Primary Completion (Actual): June 4, 2018
• Study Completion (Actual): June 4, 2018

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: February 7, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: PCS499.1005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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