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Trial registered on ANZCTR


Registration number
ACTRN12616000648426
Ethics application status
Approved
Date submitted
29/04/2016
Date registered
18/05/2016
Date last updated
18/05/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Bioequivalence study of a generic formulation of cysteamine bitartrate (Rec 0/0462, 150 mg immediate release capsules) versus the marketed Cystagon Registered Trademark, 150 mg immediate release capsules
Scientific title
Bioequivalence study of a generic formulation of cysteamine bitartrate (Rec 0/0462, 150 mg immediate release capsules) versus the marketed Cystagon Registered Trademark, 150 mg immediate release capsules, in healthy volunteers administered a single 600 mg dose
Single centre, single dose, randomised, open, two way, two period, cross-over, two stage bioequivalence study
Secondary ID [1] 289062 0
CRO-14-119
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nephropathic cystinosis 298511 0
Condition category
Condition code
Human Genetics and Inherited Disorders 298590 298590 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 298873 298873 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Test (T): Rec 0/0462, 150 mg cysteamine free base (as bitartate salt) immediate release capsules
Reference (R): Cystagon Registered Trademark, 150 mg cysteamine free base (as bitartrate salt) immediate release capsules

Two single doses of 600 mg of cysteamine base (as bitartrate salt) (one with Test and one with Reference formulations) were administered to each volunteer in two subsequent study periods, separated by wash-out intervals of 5 days.
Intervention code [1] 294568 0
Treatment: Drugs
Comparator / control treatment
Reference (R): Cystagon Registered Trademark, 150 mg cysteamine free base (as bitartrate salt) immediate release capsules
Control group
Active

Outcomes
Primary outcome [1] 298093 0
Cmax and AUC0-t of cysteamine (free base) in plasma after single dose administration of Test and Reference (composite primary outcome)
Timepoint [1] 298093 0
0 (pre-dose), 0.33 (20 min), 0.67 (40 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 16 h post-dose
Secondary outcome [1] 323151 0
AUC0-inf of cysteamine (free base) in plasma after single dose administration of Test and Reference
Timepoint [1] 323151 0
0 (pre-dose), 0.33 (20 min), 0.67 (40 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 16 h post-dose
Secondary outcome [2] 323152 0
Safety (through treatment emergent adverse events (TEAEs), vital signs (BP, HR), physical examination, body weight, laboratory parameters, ECG).
Timepoint [2] 323152 0
TEAEs throughout the entire study
Physical examination and body weight at screening (from day -21 to day -2) and final visit (day 2 of Period 2)
Vital signs:
at screening visit (from day -21 to day -2)
before IMP administration (up to 30 min before the pre-dose PK sample)
at 1, 1.5, 2, 4 , 6 and 24 h post-dose

ECG:
at screening visit (from day -21 to day -2)
before IMP administration
24 h post-dose

Secondary outcome [3] 323617 0
t1/2 of cysteamine (free base) in plasma after single dose administration of Test and Reference



Timepoint [3] 323617 0
0 (pre-dose), 0.33 (20 min), 0.67 (40 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 16 h post-dose
Secondary outcome [4] 323618 0
tmax of cysteamine (free base) in plasma after single dose administration of Test and Reference
Timepoint [4] 323618 0
0 (pre-dose), 0.33 (20 min), 0.67 (40 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 16 h post-dose
Secondary outcome [5] 323619 0
lambdaz of cysteamine (free base) in plasma after single dose administration of Test and Reference
Timepoint [5] 323619 0
0 (pre-dose), 0.33 (20 min), 0.67 (40 min), 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 16 h post-dose

Eligibility
Key inclusion criteria
1 Informed consent: signed written informed consent before inclusion in the study
2. Sex and Age: males/females of 18-45 year old inclusive
3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 beats/min, measured after 5 min at rest in the sitting position
5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
6. Lifestyle: non-smokers or ex-smokers for at least 2 years
7. Contraception and fertility (females only): females of childbearing potential had to accept using a double reliable contraceptive method (one mechanical barrier method plus another one).
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 12 leads ECG (supine position): clinically significant (CS) abnormalities or:
a. PQ interval < 120 msec or > 220 msec
b. QRS duration < 75 msec or > 120 msec
c. QTcB manual value > 440 msec (QTcB was measured manually only if QTcB > 440 msec)
2. Physical findings: CS abnormal physical findings which could interfere with the objectives of the study
3. Laboratory analyses: CS abnormal laboratory values indicative of physical illness
4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients and to penicillamine; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considered may affect the outcome of the study
5. Diseases: significant history of renal, hepatic, gastrointestinal (in particular gastrointestinal bleeding or chronic gastrointestinal disease), cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that could interfere with the aim of the study
6. Medications: medications, including over the counter (OTC) medications and herbal remedies, for 2 weeks before the start of the study, in particular current HIV or hepatitis treatment in the last three months. Hormonal contraceptives for females were allowed
7. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval was calculated as the time between the first calendar day of the month that followed the last visit of the previous study and the first day of the present study
8. Blood donation: blood donations for 3 months before this study
9. Drug, alcohol, caffeine: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010] or caffeine (>5 cups coffee/tea/day) abuse
10. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
11. Drug test: positive drug test at screening or Day -1
12. Alcohol test: positive alcohol breath test at Day -1
13. Pregnancy: pregnant or lactating women
14. Pregnancy test (all female subjects): positive pregnancy test at screening or Day -1

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
16/03/2015
Date of last participant enrolment
Anticipated
Actual
25/03/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
24
Recruitment outside Australia
Country [1] 7834 0
Switzerland
State/province [1] 7834 0

Funding & Sponsors
Funding source category [1] 293446 0
Commercial sector/Industry
Name [1] 293446 0
Recordati S.p.A., Italy
Country [1] 293446 0
Italy
Primary sponsor type
Other
Name
CROSS SA (this is the full name of the primary sponsor)
Address
Via F.A. Giorgioli 14 6864 Arzo Switzerland

Company Registered in Switzerland VAT number: CHE-103.494.047
Country
Switzerland
Secondary sponsor category [1] 292309 0
None
Name [1] 292309 0
Address [1] 292309 0
Country [1] 292309 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294929 0
Comitato Etico Cantonale della Repubblica del Canton Ticino (Cantonal Ethics Commettee of Canton Ticino)
Ethics committee address [1] 294929 0
Via Orico 5, CH-6501 Bellinzona, Switzerland
Ethics committee country [1] 294929 0
Switzerland
Date submitted for ethics approval [1] 294929 0
06/06/2014
Approval date [1] 294929 0
24/07/2014
Ethics approval number [1] 294929 0
CE2817

Summary
Brief summary
This was a single centre, single dose, randomised, open, two-way, two-period, cross-over, two-stage bioequivalence study. The objective of the study was to assess the bioequivalence of the generic formulation of cysteamine bitartrate (test formulation Rec 0/0462: T) versus the marketed formulation (reference formulation Cystagon Registered Trademark: R), in healthy male and female volunteers. The two formulations T and R were orally administered as a single dose of 600 mg (i.e. a single dose of four 150 mg capsules), under fasting conditions, in two consecutive study periods, with a wash-out interval of at least 5 days between the two administrations. Each study subject underwent 6 visits.
Trial website
Trial related presentations / publications
Not applicable
Public notes

Contacts
Principal investigator
Name 65350 0
Dr Antonio Rusca
Address 65350 0
CROSS Research S.A., Phase I Unit, Via F.A. Giorgioli 14
CH-6864 Arzo, Switzerland
Country 65350 0
Switzerland
Phone 65350 0
+41.91.640.44.50
Fax 65350 0
+41.91.640.44.51
Email 65350 0
[email protected]
Contact person for public queries
Name 65351 0
Alessandro Assandri
Address 65351 0
CROSS S.A.
Via Lavizzari, 18
CH-6850 Mendrisio, Switzerland
Country 65351 0
Switzerland
Phone 65351 0
+41.91.63.00.510
Fax 65351 0
+41.91.63.00.511
Email 65351 0
[email protected]
Contact person for scientific queries
Name 65352 0
Alessandro Assandri
Address 65352 0
CROSS S.A.
Via Lavizzari, 18
CH-6850 Mendrisio, Switzerland
Country 65352 0
Switzerland
Phone 65352 0
+41.91.63.00.510
Fax 65352 0
+41.91.63.00.511
Email 65352 0
[email protected]

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Results publications and other study-related documents

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