Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000738820
Ethics application status
Approved
Date submitted
7/06/2012
Date registered
10/07/2012
Date last updated
10/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Single Center, Randomized, Double-Blind, Single-Dose, 2-Way Crossover, Dose Escalation Study of the Pharmacokinetics and Pharmacodynamics of PX811019 Compared with triethylenetetramine dihydrochloride in Normal Healthy Volunteers
Scientific title
A Single Center, Randomized, Double-Blind, Single-Dose, 2-Way Crossover, Dose Escalation Study of the Pharmacokinetics and Pharmacodynamics of PX811019 Compared with triethylenetetramine dihydrochloride in Normal Healthy Volunteers to compare the pharmacokinetic (PK) profiles: to determine the dosing relationship of PX811019 relative to triethylenetetramine dihydrochloride and to characterize the pharmacodynamic profile of urinary copper excretion in response to the study drug.
Secondary ID [1] 280003 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics of a study drug for the treatment of diabetic complications 285912 0
Condition category
Condition code
Metabolic and Endocrine 286102 286102 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study was a Phase 1, prospective, randomized, double-blind, single-dose, two-way crossover, dose escalation with one-week washout. It was planned that up to four cohorts, with six subjects per cohort, were to be enrolled. PX811019 (TETA.Dis) or triethylenetetramine dihydrochloride (TETA.2HCl) doses were to be administered to subjects within each cohort in a single dose, at approximately molar equivalent doses of triethylenetetramine free base (approximately 166 to 167 mg free base per capsule in both treatments) in 1-, 3-, 5- or 7-capsule doses.

Cohort TETA.2HCl (mg) TETA.Dis (mg) No. Capsules
1 250 435 1
2 750 1305 3
3 1250 2175 5
4 1750 3045 7

Each subject had 3 visits to the clinic, a screening visit, and two treatment visits. Following an overnight fast, subjects were randomised to receive a single oral dose of TETA Dihydrochloride or Disuccinate on Day 1, and the alternate treatment on Day 8.
Intervention code [1] 284327 0
Treatment: Drugs
Comparator / control treatment
To compare two different drug formulations in a dose-rising study, with the dihydrochloride as the Control
Control group
Dose comparison

Outcomes
Primary outcome [1] 286578 0
The pharmacokinetic profiles of PX811019 and triethylenetetramine dihydrochloride were evaluated by analysis of plasma concentrations of triethylenetetramine and its metabolites, MAT (N1-acetyltriethylenetetramine) and DAT (N1,N10-diacetyltriethylenetetramine), following single oral doses of both formulations.
Timepoint [1] 286578 0
Blood samples for determination of plasma TETA (triethylenetetramine), MAT and DAT levels were collected on Day 1 and Day 8 at Time 0 (within 30 min prior to dosing), 5, 15, 30, 60, 90, 120 min and thereafter at 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 h post-dose on Days 2-3 and Days 9-10.
Primary outcome [2] 286603 0
Pharmacodynamic parameters were evaluated by determination of urine copper excretion following single oral doses of both formulations.
Timepoint [2] 286603 0
Urinary copper excretion was measured in urine collected on Day 1 and Day 8 at the following intervals: from -2-0 h pre-dose, and 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-16, 16-20, 20-24, 24-30, 30-36, 36-42, 42-48 h post-dose on Days 2-3 and Days 9-10.
Primary outcome [3] 286604 0
Safety evaluations included adverse event (AE) assessments, physical examinations, clinical laboratory blood tests and vital sign (blood pressure and pulse rate) assessments. Adverse events were classified as any untoward medical occurrence that emerges or worsens relative to pre-treatment baseline during drug administration or follow-up periods. AE's were assessed by the Principal Investigator who reviewed blood and urine analyses. No AE's were expected prior to treatment.
Timepoint [3] 286604 0
Evaluations were made during 48 hours following each dose (until the morning of Day 3 or Day 10).
Secondary outcome [1] 296247 0
NIL
Timepoint [1] 296247 0
NIL

Eligibility
Key inclusion criteria
Healthy adult males or females 18-60 years, inclusive, with a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and have normal renal function as calculated by a creatinine clearance >90 mL/min. Females of child-bearing potential had to have a negative pregnancy test at the Screening Visit and upon each admission to the research facility, be willing to use an effective means of birth control for four weeks prior to study medication administration, and be non-lactating. Males must have been willing to use effective barrier contraception for four weeks after study medication administration.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Adult males or females younger than 18 and older than 60 years,with a body mass index (BMI) lower than 18 and greater than 30 kg/m2, or with abnormal renal function; Pregnant females or those unwilling to take contraceptive measures; Males who were unwilling to take contraceptive measures; smokers; history of drug or alcohol abuse; participation in a clinical research study within 30 days prior to the first dose of study medication; use of iron, copper or other dietary supplements within two weeks prior to the first dose of study medication or during the study; diagnosis of iron deficiency based on levels of plasma iron, iron-binding capacity and ferritin, copper deficiency based on low levels of plasma copper or ceruloplasmin, abnormal liver function test results or a platelet count <100 x 106/L.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/09/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 4163 0
United States of America
State/province [1] 4163 0
New Jersey

Funding & Sponsors
Funding source category [1] 284785 0
Commercial sector/Industry
Name [1] 284785 0
Protemix Corporation
Country [1] 284785 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Protemix Corporation
Address
PO Box 2165, Shortland Street
Auckland 1140
Country
New Zealand
Secondary sponsor category [1] 283671 0
None
Name [1] 283671 0
Address [1] 283671 0
Country [1] 283671 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286811 0
Essex Institutional Review Board (US)
Ethics committee address [1] 286811 0
121 Main Street, Lebanon, New Jersey 08833, USA
Ethics committee country [1] 286811 0
United States of America
Date submitted for ethics approval [1] 286811 0
17/07/2007
Approval date [1] 286811 0
21/08/2007
Ethics approval number [1] 286811 0
Approval by letter from the Review Board Chariman, no actual Approval number; dated August 24, 2007. A copy can be provided if requested.

Summary
Brief summary
The objectives of this study were to compare the serum drug level profiles of PX811019 and triethylenetetramine dihydrochloride at four different doses, and to compare the effect of drug doses on urine copper excretion in normal healthy volunteers
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33819 0
Address 33819 0
Country 33819 0
Phone 33819 0
Fax 33819 0
Email 33819 0
Contact person for public queries
Name 17066 0
Dr Sally Poppitt
Address 17066 0
School of Biological Sciences
University of Auckland
Private Bag 92 019
Auckland 1142
Country 17066 0
New Zealand
Phone 17066 0
+64 (9) 630 5160
Fax 17066 0
Email 17066 0
[email protected]
Contact person for scientific queries
Name 7994 0
Dr Garth Cooper
Address 7994 0
School of Biological Sciences
University of Auckland
Private Bag 92 019
Auckland 1142
Country 7994 0
New Zealand
Phone 7994 0
+64 (9) 923 7239
Fax 7994 0
Email 7994 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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