A randomised, open-label study evaluating the pharmacokinetics, safety, and tolerability of a new once daily dose of 900mg of TETA 4HCL by comparing it against the current marketed Cuprior® formulation (450mg trientine base, twice daily) in healthy male and female participants.
This is a single centre, phase I, randomized, controlled trial with a crossover design to evaluate the pharmacokinetics (PK), safety, and tolerability of a new once daily TETA 4HCL formulation (300mg) (3x300mg trientine base tablets, OD) compared to the current marketed Cuprior® formulation (150mg) (3x150mg trientine base tablets, BD) in adult healthy male and female participants. Participants: 26 healthy participants will be enrolled to ensure 24 participants complete the study, with a balanced gender split. Treatment: Participants will be randomized to receive either the new or the current formulation of the drug, and then switch to the other formulation after a period of time (see study flow chart below). To remain in line with current EU SmPC and US PIL, being: * EU daily dose range of 450-975 mg of trientine base * US daily dose range of 150-1500mg trientine base the following treatments will be administered according to the treatment allocation schedule below: A: 900mg TETA 4HCl once a day / new formulation = 3 tablets of 300mg trientine base as a single dose B: 900mg TETA 4HCl marketed Cuprior formulation = 6 tablets of 150mg trientine base in two equally divided doses Patients will be randomised in a 1:1 ratio to either one of the following sequences: Treatment Sequence Period 1 Period 2 Sequence 1 Treatment A Treatment B Sequence 2 Treatment B Treatment A Assessments: Participants will be assessed for eligibility criteria and will be monitored closely throughout the study. Assessments will be performed during the study and at the end of the study follow-up visit. Duration: The duration of the study will be up to approximately 7 weeks, from screening to follow-up: * Screening will take place between days -28 and -2 * In-house period from D-1 to D3 with dosing on D1 of each treatment period * Follow-up will take place on D7 of Treatment Period 2 At least 5 days and a maximum of 10 days between treatment period study drug administration Objective: To evaluate the PK, safety, and tolerability of the new once daily TETA 4HCL formulation compared to the current marketed Cuprior® formulation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
3x300mg trientine base tablets as a single AM dose
6 x150mg trientine base tablets in two equally divided doses
Richmond Pharmacology Ltd
London, United Kingdom
Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
Time frame: Up to 48 hours post first dose initiation.
Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
Time frame: Up to 48 hours post first dose initiation.
Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (AUC) of TETA in Plasma
PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
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Time frame: Up to 48 hours post first dose initiation.
Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: Cmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (Time) of TETA in Plasma
PK parameters derived by non-compartmental methods including: Thalf and Tmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (Concentration) of TETA in Plasma
PK parameters derived by non-compartmental methods including: Clast and Cmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (AUC) of MAT in Plasma
PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
Time frame: Up to 48 hours post first dose initiation
Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: Cmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (Time) of MAT in Plasma
PK parameters derived by non-compartmental methods including: Thalf and Tmax..
Time frame: Up to 48 hours post first dose initiation
Pharmacokinetic Parameters (Concentration) of MAT in Plasma
PK parameters derived by non-compartmental methods including: Clast and Cmax..
Time frame: Up to 48 hours post first dose initiation
Pharmacokinetic Parameters (AUC) of DAT in Plasma
PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48.
Time frame: Up to 48 hours post first dose initiation.
Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations.
PK parameters derived by non-compartmental methods including: Cmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (Time) of DAT in Plasma
PK parameters derived by non-compartmental methods including: Thalf and Tmax.
Time frame: Up to 48 hours post first dose initiation.
Pharmacokinetic Parameters (Concentration) of DAT in Plasma
PK parameters derived by non-compartmental methods including: Clast and Cmax.
Time frame: Up to 48 hours post first dose initiation.
To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations.
The incidence, severity, and relationship of Treatment-Emergent Adverse Events (TEAEs).
Time frame: Adverse events were collected from the patient signing the ICF until the end of study/follow-up (EOS/FU) visit. The Mean (Min, Max) number of days between signing ICF and the EOS/FU visit in the study was 20.2 (16, 25). All patients completed the study.