OXN2505

Mundipharma Research GmbH

Höhenstraße 10, Limburg, United Kingdom, D-65549

Clinical Trial Contact , Mundipharma Research GmbH & Co. KG, +44 1223424900, info@contact-clinical-trial.com

Clinical Trial Contact , Mundipharma Research GmbH & Co. KG, +44 1223424900, info@contact-clinical-trial.com

No

No

No

Final

09 Feb 2015

Yes

09 Feb 2015

Yes

09 Feb 2015

No

• Quantitative analysis of intestinal microbiota as determined in stool samples of subjects treated with OXN PR compared to those treated with OxyPR. • To assess orocaecal transit time on the basis of intestinal absorption and intermediary bacterial metabolism as determined by breath tests (H2 breath test, CH4 breath test) in subjects treated with OXN PR compared to those treated with OxyPR.

1) Inclusion criteria: - Females less than one year post-menopausal had to have a negative pregnancy test prior to the first dose of study treatment, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. (A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly e.g. sterilisation, implants, injectables, combined oral contraceptives, some intrauterine devices ((IUDs), hormonal), sexual abstinence or vasectomised partner). - Subjects had to be willing and able (e.g. mental and physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled visits at pain and GE centres, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent. 2) Exclusion criteria: - Several exclusion criteria excluded subjects who were at risk from the use of IMP (e.g. those with hypersensitivity) or the study methods (please refer to protocol) 3) Dose discontinuation: The Investigator(s) or subjects themselves may have stopped study treatment at any time for safety or personal reasons. Subjects with serious diarrhoea, withdrawal syndrome, vital sign or laboratory abnormalities were also to be discontinued. 4) Safety assessments consisted of monitoring and recording all AEs and SAEs, observed or volunteered, regardless of suspected causal relationship to the IMP. This included reactions, interactions, accidents, illnesses, misuse and abuse. In addition, safety was assessed by monitoring haematology, biochemistry, and urine values, periodic measurement of vital signs and ECGs and the performance of physical examinations.

22 Jul 2013

No

No

Czech Republic: 30

Germany: 122

152

152

0

0

0

0

0

0

121

29

2

Double-blind period (overall period)

Randomised - controlled

During the Double-Blind Phase, the subject and all personnel involved with the conduct and the interpretation of the study, including the Investigators, site personnel, and the Sponsor’s staff, were blinded to the medication codes. Medication codes were not available until the completion of the study and until clinical data base lock, except in the case of emergency. Unblinding of treatment in single subject for regulatory reporting of SUSARs was done by designated drug safety personnel only

No

Oxycodone/naloxone

OXN PR

Tablet

Oral use

OXN PR and matching placebos in the DB-Phase were blinded and administered orally, prescribed q12h. Dosing was fixed and symmetrical (20, 30, 40 or 50 mg/day of oxycodone PR).

Oxycodone

OxyPR

Tablet

Oral use

OxyPR and matching placebos in the DB-Phase were blinded and administered orally, prescribed q12h. Dosing was fixed and symmetrical (20, 30, 40 or 50 mg/day of oxycodone PR).

Double-blind period

Full Analysis Population

The full analysis population is defined as all randomised subjects who receive at least one dose of IMPs and have at least one post-baseline assessments of the primary efficacy variables in each of the two treatment periods. All subjects which are part of the FAP are regarded as evaluable. In case that many subjects have only data from one treatment period a sensitivity analysis based on the reduced population will be considered

Double Blind Safety Population

The Double-blind safety population is defined as all enrolled subjects who were randomised and received at least one dose of IMP and have at least one safety assessment in the Double-Blind Phase.

OXN PR

OxyPR

Full Analysis Population

The full analysis population is defined as all randomised subjects who receive at least one dose of IMPs and have at least one post-baseline assessments of the primary efficacy variables in each of the two treatment periods. All subjects which are part of the FAP are regarded as evaluable. In case that many subjects have only data from one treatment period a sensitivity analysis based on the reduced population will be considered

Double Blind Safety Population

The Double-blind safety population is defined as all enrolled subjects who were randomised and received at least one dose of IMP and have at least one safety assessment in the Double-Blind Phase.

To assess orocaecal transit time on the basis of intestinal absorption and intermediary bacterial metabolism as determined by breath tests (H2 breath test, CH4 breath test) in subjects treated with OXN PR compared to those treated with OxyPR. Orocaecal time was measured by H2/CH4/ analysis of expired air of subjects (breath tests).

Primary

Breath test assessments at 5 minute intervals for H2/CH4: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180 + Extension by 1 hour if needed.

ANOVA with fixed terms for treatment, period and sequence and a random subject effect

OXN PR v OxyPR

127

Pre-specified

-6.42

2-sided

Events were recorded from the point at which the Informed Consent is signed until 7 days after the subject left the study. This included new AEs that were reported in the 7 days following the subject’s completion/discontinuation visit.

16.0

OXN PR

OxyPR