Clinical Trial: Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single Center, Single Dose, Open-Label, Two-Period Replicate Pilot Study to Investigate Intra-subject Variability in the Bioavailability of a Formulation Containing Chlorpromazine Hydrochloride (25

Brief Summary:

Cycle Pharmaceuticals Ltd. (Cycle) is developing an oral tablet formulation of Chlorpromazine Hydrochloride and intends to conduct bioequivalence trials to demonstrate its similarity to the RLD.

The aim of this pilot study is to investigate intrasubject variability in the bioavailability of Chlorpromazine Hydrochloride 25 mg sugar coated tablets.

Cycle aims to demonstrate that Chlorpromazine Hydrochloride has a shallow dose response curve and a wide safety margin. This will then allow for the modification of bioequivalence acceptance criteria in future pivotal studies which will reduce the number of participants required whilst still maintaining assurance of safety and efficacy.

Pilot Subjects (n): 20 Periods: 2 (2xR) Dosing: Single-dose Strength: 25 mg Test Product: N/A Reference: USL PHARMA Chlorpromazine Hydrochloride Analytes (in plasma): Chlorpromazine; 7-Hydroxychlorpromazine Bioequivalence based on 90% CI (Cmax, AUC): Standard; 80.00 - 125.00%


Detailed Summary:

This will be a single-dose, open-label, two-period replicate pilot study with orally administered chlorpromazine hydrochloride 25 mg (sugar coated tablets) conducted under fasting conditions in at least 16 healthy male and female subjects at a single study center.

Up to 20 eligible subjects will be enrolled in the study with 16 evaluable subjects to complete the study.

Analytes to be measured will be Chlorpromazine and 7-hydroxy-Chlorpromazine (free) as stipulated by FDA Guidance for assessment of bioequivalence for Chlorpromazine.


Sponsor: Cycle Pharmaceuticals Ltd.

Current Primary Outcome:

  • Maximum observed plasma concentration (Cmax) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.
  • Area under the plasma concentration versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC(0-t)) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.
  • Area under the plasma concentration versus time curve, with extrapolation to infinity (AUC(0-∞)) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to maximum observed plasma concentration (tmax) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times
  • Terminal elimination rate constant (λz) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times
  • Apparent terminal elimination half-life (t1/2.z) [ Time Frame: 0, 0.5, 1, 1.3, 1.6, 2, 2.5, 3, 4, 5, 6, 9, 12, 16, 24, 36, 48, 72 and 96 hours ]
    Time Frame = sampling times


Original Secondary Outcome: Same as current

Information By: Cycle Pharmaceuticals Ltd.

Dates:
Date Received: October 21, 2016
Date Started: November 2016
Date Completion:
Last Updated: December 13, 2016
Last Verified: December 2016