05-NEOV-001

Fresenius Kabi Deutschland GmbH

Borkenberg 14, Oberursel, Germany, 61440

Divisional Medical & Clinical Affairs Clinical Nutrition & Ketosteril, Fresenius Kabi Deutschland GmbH, trial-disclosure@fresenius-kabi.com

Divisional Medical & Clinical Affairs Clinical Nutrition & Ketosteril, Fresenius Kabi Deutschland GmbH, trial-disclosure@fresenius-kabi.com

Yes

No

No

Final

24 Sep 2010

No

Yes

18 Dec 2009

No

The primary objective of the study was to demonstrate non-inferiority of Neoven when comparing all individual plasma amino acids (AA) concentrations.

Subject protection was ensured by high medical and ethical standards in accordance with Declaration of Helsinki, Good Clinical Practice and applicable national and local laws and regulations. The signed informed consent was obtained from the legal representative of the patient prior to inclusion in the study.

30 Dec 2008

No

Yes

Germany: 6

Belgium: 3

Netherlands: 14

23

23

0

10

11

2

0

0

0

0

0

Overall trial (overall period)

Randomised - controlled

Study medication was provided as bulk products to hospital pharmacists for masking due to different strengths of study products: Neoven had a strength of 10% AAs and Vaminolact a strength of 6.5%. Neoven was diluted to a strength of 6.5 %. The unblinded pharmacists provided a blinded PN product whereas the labelling of the final product did not reveal the treatment allocation. Additional independent unblinded study monitors checked adherence to pre-defined working procedures.

Yes

Neoven

Solution for infusion

Intravenous use

Neoven was infused over a minimum of 5 days -7 days and a maximum of 10 days. Dosage was increased over the first 3 study days from 1.0 g/kg/day +/- 0.5 g/kg/day at study day 1 to 2.0 g/kg/day +/- 0.5 g/kg/day at study day 2 and 2.5 g/kg/day +/- 0.25 g/kg/day at study day 3. From Day 3 onwards the dosage was maintained until the end of study. Study treatment was to be ceased on study day 10 or in the event that enteral/oral intake exceeded 35 % of energy (calories) of PN; in which case the amount of PN intake was to be lowered correspondingly.

Vaminolact

Vaminolac, Vamin Infant

Solution for infusion

Intravenous use

Vaminolact was infused over a minimum of 5 days-7 days and a maximum of 10 days. Dosage was increased over the first 3 study days from 1.0 g/kg/day +/- 0.5 g/kg/day at study day 1 to 2.0 g/kg/day +/- 0.5 g/kg/day at study day and 2.5 g/kg/day +/- 0.25 g/kg/day at study day 3. From Day 3 onwards the dosage was maintained until the end of study. Study treatment was to be ceased on study day 10 or in the event that enteral/oral intake exceeded 35 % of energy (calories) of PN; in which case the amount of PN intake was to be lowered correspondingly.

Neoven

Vaminolact

Neoven

Vaminolact

Full Analysis Population

The Full Analysis Population for the intent-to-treat (ITT) analysis was defined as all patients in the safety population, for whom one AA profile was available after having reached full-dose for at least one day.

Amino Acid (AA) Pattern Analysis Population

The AA Pattern Analysis Population was defined as all patients in the Full Analysis Population, for whom one AA profile was available after at least 5 treatment days were performed and who completed as described in the protocol. The AA Pattern Analysis Population was the target population for the 12:6 patients allocation. It was used only for the analysis of AA Levels.

Per-Protocol (PP) Population

The PP Population was defined as all patients in the AA pattern analysis population, for whom one AA profile was available after at least 5 treatment days were performed and who completed as described in the protocol without major protocol violations. Efficacy parameters and AAs were evaluated for the PP Population.

Safety Population

The Safety Population was defined as all patients who were treated with study medication, regardless how much and how they received study treatment. The patient description and the analysis of safety were performed for this population

For each of the 23 pre-specified AAs (20 standard AAs + taurine, citrulline, and ornithine), the relative difference to the midpoint of the normal range was computed and the absolute change (relative difference at baseline compared to relative difference after last treatment) was generated. Then the sum of all 23 changes was computed.

Primary

AA plasma concentrations at baseline and after last treatment (maximum 10 days) were used to calculate the primary endpoint.

The study hypothesis was that the plasma AA profile of Neoven was not inferior to that of Vaminolact. Non-inferiority meant that, when the relative differences of all AAs from the midpoint of the normal range were considered, the sum would not be relevantly higher (inferior) to that sum observed in the Vaminolact group. For this comparison, the baseline concentrations were taken into account.

Neoven v Vaminolact

19

Pre-specified

237.4

2-sided

Standard deviation

The reporting period for adverse events (AEs) started from the time of informed consent and ended 28 (+ 7) days after last treatment

All SAEs and treatment-emergent AEs (treatment period + follow-up period), occurred in the study, are listed below.

11.1

Neoven

Vaminolact