Dose escalating PK study of PH46A

• Research type

  Research Study

• Full title

  A Phase 1, prospective, double-blind, randomised, placebo-controlled, dose escalating study to assess the safety and tolerability of single and multiple oral doses of PH46A and the effect of the fasted and fed state on pharmacokinetics of PH46A in healthy volunteers.

• IRAS ID

  146130

• Contact name

  David Bell

• Contact email

  david@biokineticeurope.com

• Sponsor organisation

  Trino Therapeutics Ltd

• Eudract number

  2013-003717-17

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  This is a first-in-man 2 part dose escalating study. Part A = single ascending dose (SAD) with separate food effect arm. Part B = multiple ascending dose (MAD) incorporating an additional blood draw for future evaluations of inflammatory biomarkers.

  Part A incorporates sentinel dosing : 2 volunteers per cohort: 1 on active treatment, 1 on placebo. No further volunteers will be dosed until at least 48 hours after dosing the second volunteer, provided there are no serious/unexplained safety issues. In Part B all volunteers may be dosed concurrently.

  Safety & PK data will be reviewed at the Safety Data Review (SDR) meetings during Part A & Part B before commencement of the next cohorts. Part B may commence prior to completing Part A.

  Study duration, 15 days in Part A, up to 22 days in Part B (excludes screening). Volunteers who participate in the food effect phase of Part A will have another period, (after 7 day washout), the same duration as the first, the difference being, they will receive a fatty breakfast on Day 1.

  Part A – starting dose = 20 mg, or placebo. Subsequent doses will be decided at the SDR meetings following each cohort, maximum dose will not exceed 900 mg.
  Part B – starting dose will be determined on the outcome of the SDR Meetings in Part A. In Part B, the study drug will be administered once daily for 7 days, with matching placebo. Subsequent doses as above, detailed in A6-2.

  Up to 48 healthy volunteers aged 18-55 in Part A - 6 cohorts of 8 volunteers.
  Up to 48 healthy volunteers aged 18-55 in Part B - 4 cohorts of 12 volunteers.
  6 datasets in Part A and 9 in Part B are required to provide sufficient data for a decision to dose escalate.

• REC name

  East of England - Cambridge East Research Ethics Committee

• REC reference

  14/EE/0023

• Date of REC Opinion

  31 Jan 2014

• REC opinion

  Favourable Opinion