E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-operative iron defieciency |
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E.1.1.1 | Medical condition in easily understood language |
Iron deficiency following an operation |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002062 |
E.1.2 | Term | Anaemia iron deficiency |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate dose proportionality of single dose Feramyl® given as 200 mg, 500 mg and 1500 mg i.v. infusion in terms of total iron in plasma
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E.2.2 | Secondary objectives of the trial |
To evaluate general safety and tolerability of Feramyl® given as 200 mg, 500 mg and 1500 mg i.v. infusion to that of 500 mg Ferinject® i.v. infusion
To evaluate the early phase iron parameters of Feramyl® given as 200 mg, 500 mg and 1500 mg i.v. infusion and compare Feramyl® 500 mg i.v. infusion to that of 500 mg Ferinject® i.v. infusion
To evaluate urine iron parameters of Feramyl® given as 200 mg, 500 mg and 1500 mg i.v. infusion and compare Feramyl® 500 mg i.v. infusion to that of 500 mg Ferinject® i.v. infusion
To characterize the pharmacokinetic parameters of Feramyl® given as 200 mg, 500 mg and 1500 mg i.v. infusion and compare Feramyl® 500 mg i.v. infusion to that of 500 mg Ferinject® i.v. infusion in terms of total iron in plasma
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent given prior to any trial procedures performed 2. Male or female aged ≥ 18years at the time of signing the informed consent 3. Cardiac surgery performed and the subject has a low mortality risk according to Euro SCORE II < 6 % 4. Anaemia defined as haemoglobin: - a.200 mg and 500 mg treatment groups: Below 13.0 g/dl (8.1 mmol/L) for males and 12.0 g/dl (7.3 mmol/L) for females and TSAT < 20 % - b.1500 mg treatment group: Below 8.1 g/dl (5 mmol/L) if bodyweight is 70-74 kg; Below 8.5 g/dl (5.3 mmol/L) if body weight is 75-79 kg; Below 9.4 g/dl (5.8 mmol/L) if body weight is 80-84 kg; Below 9.8 g/dl (6.1 mmol/L) if body weight is 85-89 kg; Below 10.3 g/dl (6.4 mmol/L) if body weight is 90 kg or above 5. Blood pressure < 145 mmHg/95 mmHg 6. Willing and able to comply with the protocol according to the investigators judgement
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E.4 | Principal exclusion criteria |
1. Body weight less than 50 kg 2.Currently experiencing an ongoing bleeding >50 ml/h for the last 3 hours before start of infusion 3.Unexplained anaemia or anaemia due to other aetiology; untreated Vitamin B12 or folate deficiency or hemoglobinopathy 4.Anticipated medical need for erythropoetin during the trial period 5.Known hypersensitivity to iron, hydroxyethylstarch or any excipients of the investigational products 6.Known drug allergy, immunological or inflammatory diseases, severe asthma, eczema or atopy 7.Preoperative anaemia treatment within 3 months prior to screening 8.Ferritin > 800 ng/ml 9.Imminent dialysis 10.Infection (T > 38.5°C or subject on non-prophylactic antibiotics) 11.Chronic liver disease or screening ALAT or ASAT above three times the upper limit of the normal range 12.Renal disease defined as proteinuria and s-creatinine > 150 µmol/l 13.Primary hematologic disease 14.Known malignant disease/cancer within the last 5 years 15.Insulin treated diabetes 16.Rheumatoid arthritis with active joint inflammation 17.History (current or past) of drug or alcohol abuse 18.Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods as required by local regulations and practice 19.Known or suspected of not being able to comply with the trial protocol (e.g. due to psychological disorders or other conditions). 20.Receipt of any investigational medicinal products within the last 90 days
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E.5 End points |
E.5.1 | Primary end point(s) |
Total iron in plasma: AUC(0-∞) and Cmax following infusion |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
General safety and tolerability measures following infusion: - Biochemistry and haematology at t= 0 (start of infusion), 8, 24, 48 and 72 hours following infusion - Blood pressure (BP) and heart rate (HR) at t= 0 (start of infusion), 15 min (end of infusion), 30 min, 60 min, 2, 3, 4, 5, 6, 7, 8, 24, 48 and 72 hours following infusion - CAEs: Infusion site reactions, hypersensitivity reactions, all-cause mortalities -Hypersensitivity reactions: To evaluate this the BP/HR at t= 15 min (end of infusion), 30 min, and 1 hour following infusion will be used - Adverse Events - TSAT, haemoglobin and ferritin at t= 0 (start of infusion), 8, 24, 48 and 72 hours following infusion - Urine iron during the four periods: 0-8 hours, 8-24 hours, 24-48 hours and 48-72 hours following infusion - Total iron in plasma: AUC(0-72), Tmax, λz, t1/2, Vz, Cl. Where t= sampling time points (0 (start of infusion), 15 min (end of infusion), 30 min, 60 min, 2, 3, 4, 5, 6, 7, 8, 24, 48 and 72 hours) following infusion.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Added to endpoints; see E.5.2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Cohort, dose ascending; only randomisation in the 500 mg dosage group |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LSLV per dose level (200 mg, 500 mg and 1500 mg). LSLV (overall) is expected October 2016. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |