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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PCS499
* Drug: Trental


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating female subjects Aged 18 to 55 years, inclusive 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 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 Subjects who were willing and able to be confined at the clinical research centre for the scheduled inpatient visits Ability to swallow multiple tablets whole Exclusion Criteria: 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 Subject had a known or suspected malignancy with the exception of basal cell carcinoma 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 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). Subject had active disease or symptoms within 7 days prior to Day -1, such as nausea, vomiting, diarrhoea, and infection Subject had undergone a hospital admission or major surgery within 30 days prior to the Screening visit Subjects who had taken part in Part 1 were not permitted to take part in Part 2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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. |