Study Comparing Once Daily Dose of 900mg of TETA 4HCL Against Cuprior® (450mg Trientine Base, Twice Daily).

NCT06128954 | Completed Phase 1 Results

• 1 other identifier: ORPH-131-012
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Wilson's Disease

Outcome Measures

Primary Outcomes (15)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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..

  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..

  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.

  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.

  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.

  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.

  Up to 48 hours post first dose initiation.

Secondary Outcomes (1)

• To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations.

  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.

Study Arms (2)

Once Daily Dose Formulation (Treatment A)

EXPERIMENTAL

1 x 900mg TETA 4HCl, new once daily formulation (3x300mg trientine base tablets as a single AM dose)

Drug: 900mg TETA 4HCl Once Daily Formulation

Cuprior® comparator (Treatment B)

ACTIVE COMPARATOR

2 x 450mg TETA 4HCl, Marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart)

Drug: 900mg TETA 4HCl Cuprior®

Interventions

900mg TETA 4HCl Once Daily Formulation DRUG

3x300mg trientine base tablets as a single AM dose

Once Daily Dose Formulation (Treatment A)

900mg TETA 4HCl Cuprior® DRUG

6 x150mg trientine base tablets in two equally divided doses

Cuprior® comparator (Treatment B)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 to 40 years
• Body weight: ≥ 50 kg
• BMI: 18.0 to 25.0 kg/m2
• Health: Generally healthy, with no clinically significant illnesses or surgeries in the past 12 weeks
• Willingness to comply with trial procedures and restrictions

You may not qualify if:

• Significant current or recurrent disease
• Acute significant disease or illness within 7 days before the start of the trial
• Clinically significant deviations in blood tests
• An estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73m2
• Positive test for alcohol, drugs of abuse, hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab)
• Pregnant or breastfeeding women
• History or regular use of tobacco or other nicotine-containing products within 6 months before the start of the trial
• Treatment with an investigational drug within 90 days or 5 half-lives (whichever is longer) or exposure to more than 3 investigational drugs within 12 months of first study drug administration
• Use of prescription medication (excluding female hormonal contraception or hormone replacement therapy)within 30 days or 5 half
• lives (whichever is longer) prior to first study drug administration, or use of over-the-counter (OTC) medication (including multivitamin, herbal, or homeopathic preparations; Paracetamol use ≤2g per day is permitted) during the 14 days or 5 half-lives of the drug (whichever is longer) before first study drug administration
• History of sensitivity/allergy to the study medications or components thereof (mannitol, colloidal anhydrous silica, glycerol dibehenate or magnesium-stearate)
• Donation or loss of 450 mL or more of blood or plasma within 16 weeks prior to first trial medication administration or intention to donate blood in the 16 weeks after completing the trial
• An inability to follow a standardised diet and meal schedule or inability to fast, as required during the trial
• Participants deemed to have difficult veins for cannulation/blood draws

Sponsors & Collaborators

• Orphalan: lead

Study Sites (1)

Richmond Pharmacology Ltd

London, SE1 1YR, United Kingdom

Location

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Carla Bennett
• Organization: Orphalan SA

carla.bennett@orphalan.com

07918380893

Study Officials

• Thomas Ashdown, MBBCh Ssc

  Richmond Pharmacology Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 13, 2023
• Study Start: January 16, 2024
• Primary Completion: February 8, 2024
• Study Completion: February 16, 2024
• Last Updated: August 15, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-08

Locations

GB (1)