In a prospective, randomised double-blind, placebo-controlled study conducted in 344 anaemic patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001).

Clinical Studies Examining QT Interval A placebo-controlled, randomized, single-dose, crossover study to evaluate the effect on the QT interval of healthy volunteers was conducted with three oral doses of voriconazole and ketoconazole.

Phase 3 randomised controlled studies 5 In randomised controlled phase 3 clinical studies, >,1000 patients have been treated with the recommended doses of 80 mg or 120 mg (536 subjects enrolled in a 28 week study and 507 subjects enrolled in a 52 weeks study).

Study FVF3192g (PIER) was a randomised, double-masked, sham-controlled, two-year study designed to assess the safety and efficacy of Lucentis in patients with neovascular AMD (79 % of the patients had minimally classic or occult AMD, 21 % had a predominantly classic CNV component).

Clinical efficacy and safety The efficacy and safety of methylnaltrexone bromide in the treatment of opioid-induced constipation in patients receiving palliative care was demonstrated in two randomised, double-blind, placebo-controlled studies.

Multi-centre, randomised, double-blind, placebo-controlled studies in 487 patients demonstrated an additive reduction of 8 to 16 % in LDL-C when 2.3 to 3.8 g Cholestagel and a statin (atorvastatin, lovastatin or simvastatin) were administered at the same time.

The palifermin clinical program in the setting of myelotoxic therapy requiring haematopoietic stem cell (HSC) support included 650 patients with haematologic malignancies enrolled in 3 randomised, placebo-controlled clinical studies and a pharmacokinetic study.

In a randomised, placebo-controlled, double-blind study (study 1, see section 5.1) the incidence of treatment-emergent cardiac ischaemia/ infarction events was higher in the Nexavar group (2.9 %) compared with the placebo group (0.4 %).

The efficacy of InductOs was demonstrated in a multinational, randomized, controlled, single-blind study of 450 patients (age range 18 to 87 years; 81% male) with open tibial shaft fractures requiring surgical management.

DULOXETINE BOEHRINGER INGELHEIM and Pelvic Floor Muscle Training (PFMT): during a 12- week blinded, randomised, controlled study, DULOXETINE BOEHRINGER INGELHEIM demonstrated greater reductions in IEF compared with either placebo treatment or with PFMT alone.

In a randomised controlled open-label study in 235 patients with Staphylococcus aureus bacteraemia (i. e, at least one positive blood culture of Staphylococcus aureus prior to receiving the first dose) 19 of 120 patients treated with Cubicin met the criteria for RIE.

The efficacy of CYMBALTA as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months.

Combination therapy in second-line treatment of metastatic colorectal cancer Data from a multicentre, randomised, controlled phase III clinical study (NO16967) support the use of Xeloda in combination with oxaliplatin for the second-line treatment of metastastic colorectal cancer.

44 The efficacy of duloxetine as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months.

A phase 3, randomized, double-blind, placebo-controlled study of SUTENT was conducted in patients with GIST who were intolerant to, or had experienced disease progression during or following treatment with, imatinib (Median maximum daily dose 800 mg).

In a multi-centre (US, Canada), parallel-group, double-blind, placebo-controlled study, 539 obese adolescent patients were randomised to receive either 120 mg orlistat (n=357) or placebo (n=182) three times daily as an adjunct to a hypocaloric diet and exercise for 52 weeks.

The efficacy of XERISTAR as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months.

In the TAP study in all lesion types, the average number of treatments per year were 3.5 in the first year after diagnosis and 2.4 in the second for the randomised placebo-controlled phase and 1.3 in the third year, 0.4 in the fourth and 0.1 in the fifth year for the open-label extension phase.

Data from an interim analysis of a multicentre, randomised, controlled phase II study (AIO KRK 0604) support the use of Xeloda at a starting dose of 800 mg/ m2 for 2 weeks every 3 weeks in combination with irinotecan and bevacizumab for the first-line treatment of patients with metastatic colorectal cancer.

The efficacy of Enbrel was assessed in a randomised, double-blind, placebo-controlled study in 211 paediatric patients aged 4 to 17 years with moderate to severe plaque psoriasis (as defined by a sPGA score ≥ 3, involving ≥ 10 % of the BSA, and PASI ≥ 12).

Adjuvant Therapy with Xeloda in colon cancer Data from one multicentre, randomised, controlled phase III clinical trial in patients with stage III (Dukes’ C) colon cancer supports the use of Xeloda for the adjuvant treatment of patients with colon cancer (XACT Study; M66001).

Study E2100 was an open-label, randomised, active controlled, multicentre clinical trial evaluating Avastin in combination with paclitaxel for locally recurrent or metastatic breast cancer in patients who had not previously received chemotherapy for locally recurrent and metastatic disease.

Treatment of azole-susceptible Oropharyngeal Candidiasis (OPC) A randomised, evaluator-blind, controlled study was completed in HIV-infected patients with azole- susceptible oropharyngeal candidiasis (most patients studied had C. albicans isolated at baseline).

In the VIP-PM study in pathological myopia, the average number of treatments per year were 3.5 in the first year after diagnosis and 1.8 in the second for the randomised placebo-controlled phase and 0.4 in the third year, 0.2 in the fourth and 0.1 in the fifth year for the open-label extension phase.

The efficacy of Forsteo in men and women (N=428) receiving sustained systemic glucocorticoid therapy (equivalent to 5 mg or greater of prednisone for at least 3 months) was demonstrated in the 18- month primary phase of a 36 month, randomised, double-blind, comparator-controlled study (alendronate 10 mg/ day).

Generalised Anxiety Disorder CYMBALTA demonstrated statistically significant superiority over placebo in five out of five studies including four randomized, double-blind, placebo-controlled acute studies and a relapse prevention study in adult patients with generalised anxiety disorder.

Study SCAB2003 was a multicentre, double-blind, double dummy, placebo and lithium-controlled, randomised fixed dose evaluation of the long-term prevention of relapse and recurrence of depression and/ or mania in patients with bipolar I disorder who had recently or were currently experiencing a major depressive episode.

e pulmonary embolism (PE). Over 4874 patients were studied in controlled Phase II and III clinical studies. Treatment of Deep Venous Thrombosis lo ng In a randomised, double-blind, clinical trial in patients with a confirmed diagnosis of acute symptomatic DVT, fondaparinux 5 mg (body weight < 50 kg), 7.5 mg (body weight ≥ 50 kg, ≤ 100 no

Generalised Anxiety Disorder XERISTAR demonstrated statistically significant superiority over placebo in five out of five studies including four randomized, double-blind, placebo-controlled acute studies and a relapse prevention study in adult patients with generalised anxiety disorder.

A multicentre randomised controlled trial comparing topiramate, stiripentol and clobazam as adjunctive therapy to valproate and clobazam in paediatric patients with Dravet’ s syndrome (SMEI) not adequately controlled with clobazam and valproate, and auxiliary pharmacogenetic study by 2010 (STP 167).

This section presents data from four randomised controlled trials in adults with rheumatoid arthritis, one study in adults with psoriatic arthritis, one study in adults with ankylosing spondylitis, one study in paediatric patients with plaque psoriasis, and four studies in adults with plaque psoriasis.

16 Combination therapy in first-line treatment of metastatic colorectal cancer Data from a multicentre, randomised, controlled phase III clinical study (NO16966) support the use of Xeloda in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer.

The safety and efficacy of conversion from calcineurin inhibitors to Rapamune in maintenance renal transplant patients (6-120 months after transplantation) was assessed in a randomised, multicentre, controlled trial, stratified by calculated GFR at baseline (20-40 mL/ min vs > 40 mL/ min).

Breast cancer A randomised placebo-controlled trial, the Women’s Health Initiative study (WHI), and epidemiological studies, including the Million Women Study (MWS), have reported an increased risk of breast cancer in women taking oestrogens, oestrogen-progestagen combinations or tibolone for HRT for several years (see section 4.8).

Two randomised, placebo-controlled, double-masked, multicentre, 24-month studies (BPD OCR 003 AMD, or Verteporfin in Photodynamic Therapy-AMD [ VIP-AMD ], and BPD OCR 013, or Visudyne in Occult Choroidal Neovascularisation [ VIO ]) were conducted in patients with AMD characterised by occult with no classic subfoveal CNV.

In a second outpatient study with two week run in baseline period with placebo and a randomised, double blind, placebo controlled, parallel group treatment period of 3 weeks, the rate of patients who showed a clinically significant improvement in both quality of sleep and morning alertness was 26 % in the Circadin group as compared to 15 % in the placebo group.

Induction treatment in severe active Crohn’ s disease The efficacy of a single dose treatment with infliximab was assessed in 108 patients with active Crohn’ s disease (Crohn’ s Disease Activity Index (CDAI) ≥ 220 ≤ 400) in a randomised, double- blinded, placebo-controlled, dose-response study.

Age-related Macular Degeneration with predominantly classic subfoveal lesions Visudyne has been studied in two randomised, placebo-controlled, double-masked, multicentre studies (BPD OCR 002 A and B or Treatment of Age-related Macular Degeneration with Photodynamic Therapy [ TAP ]).

Efficacy in adult patients with pulmonary arterial hypertension (PAH) A randomised, double-blind, placebo-controlled study was conducted in 278 patients with primary pulmonary hypertension, PAH associated with connective tissue disease (CTD), and PAH following surgical repair of congenital heart lesions.

The REIN study, a multicenter randomized, double-blind parallel group, placebo-controlled study aimed at assessing the effect of treatment with ramipril on the rate of decline of glomerular function rate (GFR) in 352 normotensive or hypertensive patients (18-70 years old) suffering from mild (i. e. mean urinary protein excretion > 1 and < 3 g/ 24 h) or severe proteinuria (≥ 3 g/ 24 h) due to chronic non-diabetic nephropathy.

In an outpatient study with 2 week run-in baseline period with placebo, a randomised, double blind, placebo controlled, parallel group treatment period of 3 weeks and 2 week withdrawal period with placebo, the rate of patients who showed a clinically significant improvement in both quality of sleep and morning alertness was 47 % in the Circadin group as compared to 27 % in the placebo group.

The efficacy of Enbrel versus other systemic therapies in patients with moderate to severe psoriasis (responsive to other systemic therapies) has not been evaluated in studies directly comparing Enbrel with other systemic therapies. Instead, the safety and efficacy of Enbrel were assessed in four randomised, double-blind, placebo-controlled studies.

This section presents data from four randomised controlled trials in adults with rheumatoid arthritis, one study in polyarticular juvenile idiopathic arthritis, one study in adults with psoriatic arthritis, one study in adults with ankylosing spondylitis, one study in paediatric patients with plaque psoriasis, and four studies in adults with plaque psoriasis.

Efficacy as monotherapy has been evaluated in one randomised, double-blind, placebo-controlled study lasting 2 years (AFFIRM study) in relapsing-remitting MS patients who had experienced at least 1 clinical relapse during the year prior to entry and had a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5. Median age was 37 years, with a median disease duration of 5 years.

Use of peginterferon as long term maintenance monotherapy (unapproved use) In a randomised, controlled US study (HALT-C) of HCV non-responder patients with varied degrees of fibrosis where 3.5 years of treatment with 90 micrograms/ week of Pegasys monotherapy was studied, no significant reductions were observed in the rate of fibrosis progression or related clinical events.

The efficacy and safety of a daily dose of 0.25 mg/ kg to 10 mg adefovir dipivoxil in children (aged from 2 to < 18 years) was examined in a double-blind, randomised, placebo-controlled study in 173 paediatric patients (115 on adefovir dipivoxil, 58 on placebo) who had HBeAg positive chronic hepatitis B, serum ALT levels ≥ 1.5 x upper limit of normal (ULN) and compensated liver disease.

The safety and efficacy of Remicade were assessed in two (ACT 1 and ACT 2) randomized, double- blind, placebo-controlled clinical studies in adult patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore 2) with an inadequate response to conventional therapies [ oral corticosteroids, aminosalicylates and/ or immunomodulators (6-MP, AZA) ].

In a randomised, 48-week double-blind, controlled study of tenofovir disoproxil 245 mg (as fumarate) in patients co-infected with HIV-1 and chronic hepatitis B with prior lamivudine experience (study ACTG 5127), the mean serum HBV DNA levels at baseline in patients randomised to the tenofovir

Recent myocardial infarction The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomised, controlled, multinational, double-blind study in 14,703 patients with acute myocardial infarction and signs, symptoms or radiological evidence of congestive heart failure and/ or evidence of left ventricular systolic dysfunction (manifested as an ejection fraction ≤ 40 % by radionuclide ventriculography or ≤ 35 % by echocardiography or ventricular contrast angiography).

ECOG E3200 This was a phase III randomised, active-controlled, open-label study investigating Avastin 10 mg/ kg in combination with leucovorin with 5-fluorouracil bolus and then 5-fluorouracil infusional, with IV oxaliplatin (FOLFOX-4), administered on a 2-weekly schedule in previously-treated patients (second line) with advanced colorectal cancer.