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Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Various Formulations and Doses of PWT-143

Phase 1
Completed
Conditions
Malignancies
Interventions
Registration Number
NCT02521389
Lead Sponsor
MEI Pharma, Inc.
Brief Summary

This single center first in human (FIH) study will comprise 2 parts; Part 1 will consist of 3 sequential dose groups (Groups A, B and C) and Part 2 will consist of 1 dose group (Group A). There will be an option to include 2 additional dose groups in Part 1 (Groups D and E) to assess alternative dose levels or formulations, if required.

In each study part, each subject will receive a single dose of investigational medicinal product PWT-143 in each of 2 study periods (total of 2 single doses).

Detailed Description

This first-in-human study will comprise 2 parts. In each part, each subject will receive a single dose of investigational medicinal product (IMP) in each of 2 study periods (total of 2 single doses).

Part 1 (Single Ascending Dose) This is an open-label, single dose design. It is planned to enroll up to 3 sequential groups (Groups A, B and C), comprising 3, 6 and 6 subjects, respectively, with 2 optional additional groups (Groups D and E), each comprising 6 subjects, to assess alternative dose levels or formulations (described below), if required.

The starting dose, dose increments and dose range are based on available pre-clinical data. Current planned dose levels are: 10, 30, 60, 90 and 150 mg (dose levels 1, 2, 3, 4 and 5, respectively); however, doses above 10 mg will be selected based on a review of emerging data from this study.

It is planned to use Formulation 1 for dose administration in Part 1 (Group A), selected from 3 test formulations. However, based on the exposure seen in the emerging data, an alternative formulation may be selected for dose comparison or escalation.

Part 2 (Food Effect Assessment) This is an open-label, randomised, single dose, 2-way crossover design to assess a selected formulation of PWT-143 in the fed and fasted states. Subjects will be administered a single dose of investigational medicinal product in the fed and fasted states across 2 study periods according to the randomisation schedule. There will be a minimum washout period for PWT-143 of 7 days between dose administrations in Periods 1 and 2.

It is planned that 1 group comprising 8 subjects will participate in Part 2. Subjects will be considered evaluable if they have received both treatments (ie, fed and fasted) and have completed safety assessments and PK sampling up to 24 h post-dose.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
35
Inclusion Criteria
  1. Healthy males
  2. Age 18 to 65 years of age
  3. Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
  4. Part 2 only: Must be able to consume all food items in a standard high fat breakfast and/or have no conditions or surgery (eg, cholecystectomy) that could affect their ability to eat the high fat breakfast
  5. Must be willing and able to communicate and participate in the whole study
  6. Must be willing to provide voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care
  7. Must agree to use an adequate method of contraception
Exclusion Criteria
  1. Healthy males
  2. Age 18 to 65 years of age
  3. Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
  4. Part 2 only: Must be able to consume all food items in a standard high fat breakfast and/or have no conditions or surgery (eg, cholecystectomy) that could affect their ability to eat the high fat breakfast
  5. Must be willing and able to communicate and participate in the whole study
  6. Must be willing to provide voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care
  7. Must agree to use an adequate method of contraception

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Part 1PWT-1433 sequential groups (Groups A, B and C), comprising 3, 6 and 6 subjects, respectively, with 2 optional additional groups (Groups D and E), each comprising 6 subjects, to assess alternative dose levels or formulations (described below), if required.
Part 2PWT-143Single dose, 2-way crossover design to assess a selected formulation of PWT-143 in the fed and fasted states in 8 subjects.
Primary Outcome Measures
NameTimeMethod
The number of participants with and types of Adverse Events5 months
Secondary Outcome Measures
NameTimeMethod
Tmax (time from dosing at which Cmax is determined)5 months
AUC (area under the concentration time curve)5 months
Cmax (maximum observed plasma concentration)5 months

Trial Locations

Locations (1)

Quotient Clinical

🇬🇧

Ruddington, Nottingham, United Kingdom

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