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

Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of Various Formulations of PWT-143 in Healthy Subjects

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).

Study Overview

• Status: Completed
• Conditions: Malignancies
• Intervention / Treatment: Drug: PWT-143

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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.	Drug: PWT-143; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) delta inhibitor
Experimental: Part 2; Single dose, 2-way crossover design to assess a selected formulation of PWT-143 in the fed and fasted states in 8 subjects.	Drug: PWT-143; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) delta inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of participants with and types of Adverse Events	5 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Tmax (time from dosing at which Cmax is determined)	5 months
Cmax (maximum observed plasma concentration)	5 months
AUC (area under the concentration time curve)	5 months

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.
• Collaborators: Quotient Clinical
• Investigators: Principal Investigator: Pui Leung, MBChB, Study Principal Investigator

Publications and helpful links

General Publications

• Moreno O, Butler T, Zann V, Willson A, Leung P, Connor A. Safety, Pharmacokinetics, and Pharmacodynamics of ME-401, an Oral, Potent, and Selective Inhibitor of Phosphatidylinositol 3-Kinase P110delta, Following Single Ascending Dose Administration to Healthy Volunteers. Clin Ther. 2018 Nov;40(11):1855-1867. doi: 10.1016/j.clinthera.2018.09.006. Epub 2018 Oct 26.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2015
• Primary Completion (Actual): February 24, 2017
• Study Completion (Actual): February 24, 2017

Study Registration Dates

• First Submitted: August 4, 2015
• First Submitted That Met QC Criteria: August 11, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: August 28, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PWT-143