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Trial registered on ANZCTR


Registration number
ACTRN12619000171112
Ethics application status
Approved
Date submitted
30/01/2019
Date registered
5/02/2019
Date last updated
13/03/2020
Date data sharing statement initially provided
5/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetic study of two orally formulated modified release tablets of Ferrous Sulfate 325mg and Sodium Ascorbate 562.4 mg in healthy volunteers under fasting and fed conditions.
Scientific title
Randomized, Single Dose, Two Way, Cross-Over Open-Label Study To Determine The Pharmacokinetic Parameters Of AFT Pharmaceuticals Ltd Test Product Ferro-C (325 mg Ferrous Sulfate And 562.4 mg Sodium Ascorbate Per Modified Release Tablet) Relative To BGP Products Pty Ltd Reference Product FERRO-GRAD C® (325 mg Ferrous Sulfate And 562.4 mg Sodium Ascorbate Per Modified Release Tablet), After Oral Administration In 24 Healthy Adult Volunteers Under Fasting and Fed Conditions
Secondary ID [1] 297240 0
IRAS-T0119/02 & 03
Universal Trial Number (UTN)
U1111-1227-6509
Trial acronym
Not applicable
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Anaemia 311310 0
Condition category
Condition code
Blood 309942 309942 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Test Product: Ferro-C, Dried ferrous sulfate 325mg and sodium ascorbate 562.4mg per modified release tablet
Administered as single dose of one modified release tablet given orally with 240 mL of water under the supervision of the study site staff.
There will be a washout period of at least 7 days from completion of dosing in one period to the start of dosing in the next period.
During the fasting condition study, subjects will be randomly allocated to either test product treatment or the reference product treatment, following a wash out period, subjects will enter into another treatment phase to complete the cross over.

During the fed condition study, the same procedure will apply.

Under Fasting Condition: Participants will be fasted for at least 10 hours overnight before dosing and for 4 hours after dosing. Water will be restricted for 1 hour pre-dose and 1 hour post-dose. Participants will be provided with standard meals during their clinic stay from approximately 4 and 12 hours post dose. Also a snack will provided approximately at 8 hours after the study drug administration.
Under Fed Condition: Subjects will be fasted at least 10 hours overnight and receive a standard breakfast served 30 minutes prior to study drug administration. This breakfast will supply around 927 kcal, about 50% of which are fat calories. Subjects will eat this meal in 30 minutes and study drug will be administered 30 mins after the start of meal. No additional food will be allowed for at least 5 hours post-dose.
Intervention code [1] 313493 0
Treatment: Drugs
Comparator / control treatment
Reference Products: Ferro-Grad C®: Dried ferrous sulfate 325mg and sodium ascorbate 562.4mg per modified release tablet
Administered as single dose of one modified release tablet given orally with 240 mL of water.
Under Fasting Condition: Participants will be fasted for at least 10 hours overnight before dosing and for 4 hours after dosing. Water will be restricted for 1 hour pre-dose and 1 hour post-dose. Participants will be provided with standard meals during their clinic stay from approximately 4 and 12 hours post dose. Also a snack will provided approximately at 8 hours after the study drug administration.
Under Fed Condition: Subjects will be fasted at least 10 hours overnight and receive a standard breakfast served 30 minutes prior to study drug administration. This breakfast will supply around 927 kcal, about 50% of which are fat calories. Subjects will eat this meal in 30 minutes and study drug will be administered 30 mins after the start of meal. No additional food will be allowed for at least 5 hours post-dose.
Control group
Active

Outcomes
Primary outcome [1] 318861 0
To evaluate and determine the pharmacokinetics parameters (Cmax, AUC0-t, AUC0-inf and Tmax) of serum total iron between test and reference products under fasting conditions.
Timepoint [1] 318861 0
Blood samples will be collected before dosing (at -12.00, -6.00 and -1.00 hours) and at the following times after the dose: (1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 14.00, 16.00, 20.00 and 24.00 hours).
Secondary outcome [1] 366280 0
To compare the safety and tolerability of the treatments
Safety will be evaluated during each study period, and for 7 days following study drug administration.
An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments, including measurements of vital signs (blood pressure, heart rate, respiratory rate) and body temperature.
At screening and at the end of each study period an additional blood sample will be taken for haematology, biochemistry and serological assessments (only in screening).
Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and at a final follow-up phone call.
Timepoint [1] 366280 0
Safety will be evaluated during each study period, and for 7 days following study drug administration.

Eligibility
Key inclusion criteria
Male or female subjects aged between 18 and 50 years, inclusive, on the day of consent.
Voluntarily provide written informed consent before the initiation of any study-related procedures.
Have a Body Mass Index (BMI) between 18.5 and 30.0 kg/m2.
Have no significant disease (asthma, peptic or gastric ulcer, sinusitis, pharyngitis, gastrointestinal disease, pulmonary disease, renal disorder (impaired renal function), hepatic disorder (impaired hepatic function), cardiovascular disorder, neurological disease such as epilepsy, haematological disorders or diabetes, psychiatric, infective, dermatologic or immunological disorders) as determined by medical history, physical examination and laboratory tests.
Have negative HIV and hepatitis B & C test results.
Be able and willing to abstain from caffeine-containing beverages (e.g. coffee, soda, energy drinks or tea), caffeine-containing food (e.g. chocolate), and alcohol for at least 24 hours prior to study drug administration until the last study sample is collected in each period.
Be able and willing to abstain from any food or beverages containing grapefruit for at least 7 days prior to study drug administration until the last study sample is collected in each period.
Be able and willing to abstain from prescription drugs (not including oral contraceptives and the study medication) within at least 14 days prior to study drug administration and during the study or have used over-the-counter drugs or herbal products within at least 7 days prior to study drug administration and during the study.
Be able and willing to abstain from vitamins taken for nutritional purposes for at least 2 days prior to study drug administration until the last study sample is collected in each period.
Be able and willing to abstain from smoking throughout the whole duration of the study
Have a medically acceptable normal 12-lead ECG.
No parenteral or oral iron for last 2 weeks before study drug administration.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Female who are pregnant or nursing (not applicable for male subjects).
Female of childbearing potential who are unwilling to take adequate contraceptive precautions, i.e., a hormonal contraceptive, an intrauterine device, double-barrier method, or abstinence. A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone a partial or total hysterectomy or surgical sterilisation, e.g. bilateral tubal ligation, bilateral oophorectomy (not applicable for male subjects).
Female of childbearing potential who are unwilling to undergo a urine pregnancy test (not applicable for male subjects).
Have an alcohol intake in excess of 14 units per week for females and 21 units per week for males.
Have a history of drug abuse or positive test results for drug abuse during screening.
Unwilling to abstain from smoking throughout the whole duration of the study
Unable and refuse to abstain the used prescription drugs (not including oral contraceptives and the study medication) within at least 14 days prior to study drug administration and during the study or have used over-the-counter drugs or herbal products within at least 7 days prior to study drug administration and during the study.
Unable and refuse to abstain the use of vitamins taken for nutritional purposes within
at least 2 days prior to study drug administration until the last study sample is collected in each period.
Unable and refuse to abstain to consume grapefruit containing foods or beverages within at least 7 days or caffeine containing foods or beverages within at least 24 hours prior to study drug administration until the last study sample is collected in each period.
Currently, or in last 80 days, participating in a clinical trial involving another study drug.
Have donated blood or blood products within 60 days prior to study drug administration.
Have a clinically significant abnormal laboratory test (as determined by the Investigator), Hb test which deviated outside the 5% of below limit of reference range or laboratory results of liver or kidney function tests (creatinine, urea and ALP will be accepted if below reference range, total protein and albumin accepted if above reference range) are outside the reference range
Be on a special diet (for example is vegetarian).
Unable and refuse to abstain to engage in strenuous exercise within at least 24 hours prior to study drug administration until the last sample is collected in each study period.
Have at screening examination a pulse outside the normal range of (60-100 beat per minute) or a body temperature outside the normal range of (35.0-37.2 degrees celsius) or a respiratory rate outside the normal range of (14-20 breath per minute) or a sitting blood pressure less than 100/60 mm Hg or more than or equal to 140/90 mm Hg.
Unable and refuse to abstain to consume any beverages or food containing alcohol for at least 24 hours prior to study drug administration until the last study sample is collected in each period.
Have a history of difficulties in swallowing or any gastrointestinal disease which could affect the drug absorption.
Suffering from any other diseases or condition which, in the opinion of the investigator, means that it would not be in the participant’s best interests to participate in this study.
Subject is a heavy smoker (more than 10 cigarettes per day).
Acute infection within one week preceding study drug administration.
Subject having relative or absolute iron deficiency or iron overload.
Subject having documented bleeding disorders, acute bleeding or recently documented haemorrhage.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Not applicable
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
PK Analysis:
For each subject baseline total iron level will be measured before dosing (-12.00, -6.00 and -1.00 hours). The mean of the pre-dose total iron levels should be used for the baseline adjustment of the post-dose levels. If a negative serum concentration value results after baseline correction, this should be set to zero.
The concentration at zero time will be set as zero for all subjects after baseline correction.
On the basis of the baseline-corrected concentration-time data, the following pharmacokinetic parameters will be estimated for serum total iron from the serum baseline-corrected concentration against time data:
AUC0-t: The area under the baseline-corrected serum concentration versus time curve from time zero to the last measurable concentration, as calculated by the linear trapezoidal method.
AUC0-inf: The area under the baseline-corrected serum concentration versus time curve, from zero to infinity. AUC0-inf is calculated as the sum of the AUC0-t plus the ratio of the last baseline-corrected serum concentration to the elimination rate constant (Ct/Kel).
Cmax: Maximum measured baseline-corrected serum concentration directly obtained from the experimental data of serum concentration versus time curves, without interpolation.
Tmax: Time of maximum measured baseline-corrected serum concentration. If the maximum value occurs at more than one point, Tmax is defined as the time of the first occurrence.
The mean of the values obtained prior to dosing (at -12.00, -6.00 and -1.00 hours) will serve as the baseline values for which serum concentrations will be corrected.
The actual times of blood sampling will be used for these calculations as per internal SOPs, DMU-001
Baseline-corrected serum concentrations for each formulation at each time and the pharmacokinetic parameters will be summarized using standard descriptive statistics, including means, medians, geometric means, ranges, inter-quartile ranges, standard deviations, coefficient of variations and standard error of means.
Descriptive statistics, including the means, standard deviations, standard error of the mean and coefficient of variation, shall be reported for the serum concentrations. For pharmacokinetic parameters, arithmetic means, standard deviations, standard error of the mean, minimum, median, maximum, coefficient of variation, inter-quartile ranges and geometric means shall be reported.
The bioavailability of the pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf will be determined from the 90% confidence intervals for the ratios of the parameters calculated using the residual variance from an ANOVA of loge transformed values. The ANOVA model will include terms for participant, period and formulation.
Tmax will be summarized as medians with inter-quartile ranges and compared between treatments using Wilcoxon signed rank tests.

Safety Analysis:
AEs will be collected for all randomized participants and will be listed with type of AE, severity and relationship for each treatment group, using the safety population. Adverse events data will be summarized for each formulation using frequencies and percentages (% of participants with each specific AE).
The haematology and biochemistry data collected pre-study and after each study period will be summarized descriptively using means, medians, standard deviations, ranges and frequencies and percentages as appropriate. Individual values outside normal ranges and considered clinically significant will be individually listed. Comparisons of the haematology and biochemistry measures associated with each treatment may be compared between treatments using repeated measures by ANOVA using Systat program.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/05/2019
Actual
27/04/2019
Date of last participant enrolment
Anticipated
1/08/2019
Actual
4/05/2019
Date of last data collection
Anticipated
1/10/2019
Actual
11/07/2019
Sample size
Target
24
Accrual to date
Final
25
Recruitment outside Australia
Country [1] 21229 0
Jordan
State/province [1] 21229 0
Amman, Jordan

Funding & Sponsors
Funding source category [1] 301798 0
Commercial sector/Industry
Name [1] 301798 0
AFT Pharmaceuticals Ltd
Country [1] 301798 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
AFT Pharmaceuticals Ltd.
Address
Level 1, 129 Hurstmere Road, Takapuna, Auckland 0622 New Zealand
Country
New Zealand
Secondary sponsor category [1] 301538 0
None
Name [1] 301538 0
Address [1] 301538 0
Country [1] 301538 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302507 0
IRB of IPRC (International Pharmaceutical Research Centre)
Ethics committee address [1] 302507 0
Ethics committee country [1] 302507 0
Jordan
Date submitted for ethics approval [1] 302507 0
22/02/2019
Approval date [1] 302507 0
03/02/2019
Ethics approval number [1] 302507 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90450 0
Dr Majdi Abu Awida, M.D.,
Address 90450 0
International Pharmaceutical Research Center (IPRC)
1 Queen Rania Street, Sport City Circle, Amman 11196 Jordan
Country 90450 0
Jordan
Phone 90450 0
+ 962-6-5627648
Fax 90450 0
+ 962-6-5627654
Email 90450 0
iprc@iprc.com.jo
Contact person for public queries
Name 90451 0
Jennifer Zhang
Address 90451 0
AFT Pharmaceuticals Ltd.
Level 1, 129 Hurstmere Road, Takapuna, Auckland 0622, New Zealand
Country 90451 0
New Zealand
Phone 90451 0
+64 9 488 0232 ect 710
Fax 90451 0
+ 64 9 488 0234
Email 90451 0
jenniferz@aftpharm.com
Contact person for scientific queries
Name 90452 0
Jennifer Zhang
Address 90452 0
AFT Pharmaceuticals Ltd.
Level 1, 129 Hurstmere Road, Takapuna, Auckland 0622, New Zealand
Country 90452 0
New Zealand
Phone 90452 0
+64 9 488 0232 ect 710
Fax 90452 0
+ 64 9 488 0234
Email 90452 0
jenniferz@aftpharm.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.