Wilson's Disease
Conditions
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.
Detailed description
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.
Interventions
DRUG900mg TETA 4HCl Once Daily Formulation
3x300mg trientine base tablets as a single AM dose
DRUG900mg TETA 4HCl Cuprior®
6 x150mg trientine base tablets in two equally divided doses
Sponsors
Orphalan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | 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. |
| Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | 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. |
| Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | 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. |
| Pharmacokinetic Parameters (AUC) of TETA in Plasma | Up to 48 hours post first dose initiation. | 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. |
| Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Cmax. |
| Pharmacokinetic Parameters (Time) of TETA in Plasma | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Thalf and Tmax. |
| Pharmacokinetic Parameters (Concentration) of TETA in Plasma | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Clast and Cmax. |
| Pharmacokinetic Parameters (AUC) of MAT in Plasma | Up to 48 hours post first dose initiation | 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. |
| Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Cmax. |
| Pharmacokinetic Parameters (Time) of MAT in Plasma | Up to 48 hours post first dose initiation | PK parameters derived by non-compartmental methods including: Thalf and Tmax.. |
| Pharmacokinetic Parameters (Concentration) of MAT in Plasma | Up to 48 hours post first dose initiation | PK parameters derived by non-compartmental methods including: Clast and Cmax.. |
| Pharmacokinetic Parameters (AUC) of DAT in Plasma | Up to 48 hours post first dose initiation. | 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. |
| Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Cmax. |
| Pharmacokinetic Parameters (Time) of DAT in Plasma | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Thalf and Tmax. |
| Pharmacokinetic Parameters (Concentration) of DAT in Plasma | Up to 48 hours post first dose initiation. | PK parameters derived by non-compartmental methods including: Clast and Cmax. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | The incidence, severity, and relationship of Treatment-Emergent Adverse Events (TEAEs). |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORThomas Ashdown, MBBCh Ssc
Richmond Pharmacology Limited
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Once Daily TETA 4HCl Formulation, Followed by Twice Daily Cuprior® Formulation Participants first received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart) for 3 days. | 13 |
| Sequence 2: Twice Daily Cuprior® Formulation, Followed by Once Daily TETA 4HCl Formulation Participants first received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose) for 3 days. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Sequence 2: Twice Daily Cuprior® Formulation, Followed by Once Daily TETA 4HCl Formulation | Total | Sequence 1: Once Daily TETA 4HCl Formulation, Followed by Twice Daily Cuprior® Formulation |
|---|---|---|---|
| Age, Continuous | 28.5 years STANDARD_DEVIATION 5.91 | 27.4 years STANDARD_DEVIATION 5.85 | 26.4 years STANDARD_DEVIATION 5.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 24 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 15 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 3 / 26 | 3 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
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.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of DAT in Plasma | AUCinf | 6285.164 h*ng/mL | Geometric Coefficient of Variation 51.082 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of DAT in Plasma | AUC 24 | 4966.208 h*ng/mL | Geometric Coefficient of Variation 56.026 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of DAT in Plasma | AUCinf | 8324.132 h*ng/mL | Geometric Coefficient of Variation 50.17 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of DAT in Plasma | AUC 24 | 6310.627 h*ng/mL | Geometric Coefficient of Variation 55.882 |
Primary
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
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of MAT in Plasma | AUCinf | 23383.874 h*ng/mL | Geometric Coefficient of Variation 27.676 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of MAT in Plasma | AUC 24 | 19327.926 h*ng/mL | Geometric Coefficient of Variation 29.416 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of MAT in Plasma | AUCinf | 30655.260 h*ng/mL | Geometric Coefficient of Variation 22.052 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of MAT in Plasma | AUC 24 | 25318.882 h*ng/mL | Geometric Coefficient of Variation 22.149 |
Primary
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.
Time frame: Up to 48 hours post first dose initiation.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of TETA in Plasma | AUCinf | 13561.621 h*ng/mL | Geometric Coefficient of Variation 48.627 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (AUC) of TETA in Plasma | AUC 24 | 12668.493 h*ng/mL | Geometric Coefficient of Variation 49.498 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of TETA in Plasma | AUCinf | 11778.232 h*ng/mL | Geometric Coefficient of Variation 45.404 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (AUC) of TETA in Plasma | AUC 24 | 10971.720 h*ng/mL | Geometric Coefficient of Variation 45.807 |
Primary
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.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of DAT in Plasma | Clast | 22.899 ng/mL | Geometric Coefficient of Variation 33.64 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of DAT in Plasma | Cmax | 443 ng/mL | Geometric Coefficient of Variation 64 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of DAT in Plasma | Clast | 30.100 ng/mL | Geometric Coefficient of Variation 37.799 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of DAT in Plasma | Cmax | 451 ng/mL | Geometric Coefficient of Variation 63 |
Primary
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
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of MAT in Plasma | Clast | 67.119 ng/mL | Geometric Coefficient of Variation 32.127 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of MAT in Plasma | Cmax | 2031 ng/mL | Geometric Coefficient of Variation 32 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of MAT in Plasma | Clast | 81.886 ng/mL | Geometric Coefficient of Variation 36.08 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of MAT in Plasma | Cmax | 2059 ng/mL | Geometric Coefficient of Variation 23 |
Primary
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.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of TETA in Plasma | Clast | 16.040 ng/mL | Geometric Coefficient of Variation 45.71 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Concentration) of TETA in Plasma | Cmax | 3436 ng/mL | Geometric Coefficient of Variation 41 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of TETA in Plasma | Clast | 17.382 ng/mL | Geometric Coefficient of Variation 44.905 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Concentration) of TETA in Plasma | Cmax | 1567 ng/mL | Geometric Coefficient of Variation 45 |
Primary
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.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of DAT in Plasma | Thalf | 11.053 Hours | Geometric Coefficient of Variation 14.335 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of DAT in Plasma | Tmax | 5.3587 Hours | Geometric Coefficient of Variation 14.9105 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of DAT in Plasma | Thalf | 8.529 Hours | Geometric Coefficient of Variation 11.086 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of DAT in Plasma | Tmax | 12.3653 Hours | Geometric Coefficient of Variation 20.6338 |
Primary
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
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of MAT in Plasma | Thalf | 13.852 Hours | Geometric Coefficient of Variation 27.03 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of MAT in Plasma | Tmax | 3.8785 Hours | Geometric Coefficient of Variation 26.481 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of MAT in Plasma | Thalf | 9.045 Hours | Geometric Coefficient of Variation 16.633 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of MAT in Plasma | Tmax | 13.0875 Hours | Geometric Coefficient of Variation 12.7188 |
Primary
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.
Population: Crossover design, participants exposed to both treatments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of TETA in Plasma | Thalf | 15.593 Hours | Geometric Coefficient of Variation 30.461 |
| Once Daily Dose Formulation (Treatment A) | Pharmacokinetic Parameters (Time) of TETA in Plasma | Tmax | 0.8874 Hours | Geometric Coefficient of Variation 73.6544 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of TETA in Plasma | Thalf | 8.643 Hours | Geometric Coefficient of Variation 49.617 |
| Cuprior® Comparator (Treatment B) | Pharmacokinetic Parameters (Time) of TETA in Plasma | Tmax | 1.9438 Hours | Geometric Coefficient of Variation 116.0599 |
Primary
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 19327.926 h*ng/mL |
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 23383.874 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 25318.882 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 30655.260 h*ng/mL |
Primary
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 4966.208 h*ng/mL |
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 6285.164 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 6310.627 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 8324.132 h*ng/mL |
Primary
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 12668.493 h*ng/mL |
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 13561.621 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | AUC 24 | 10971.720 h*ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | AUCinf | 11778.232 h*ng/mL |
Primary
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | 2030.958 ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | 2058.668 ng/mL |
Primary
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | 443.208 ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | 450.705 ng/mL |
Primary
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | 3435.621 ng/mL |
| Cuprior® Comparator (Treatment B) | Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | 1567.145 ng/mL |
Secondary
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with treatment-related TEAEs. | 2 Participants |
| Once Daily Dose Formulation (Treatment A) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with clinically significant changes in laboratory safety tests | 0 Participants |
| Once Daily Dose Formulation (Treatment A) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with morphological and/or rhythm abnormalities on electrocardiogram (ECG) | 0 Participants |
| Once Daily Dose Formulation (Treatment A) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with clinically significant changes in vital signs | 0 Participants |
| Cuprior® Comparator (Treatment B) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with clinically significant changes in vital signs | 1 Participants |
| Cuprior® Comparator (Treatment B) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with treatment-related TEAEs. | 1 Participants |
| Cuprior® Comparator (Treatment B) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with morphological and/or rhythm abnormalities on electrocardiogram (ECG) | 0 Participants |
| Cuprior® Comparator (Treatment B) | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | Participants with clinically significant changes in laboratory safety tests | 0 Participants |