Control efficacy reduction

A meta-analysis of placebo-controlled studies by Levin and Lehman (1991) showed that desipramine produced greater cocaine abstinence than placebo. Although a more recent review did not concur (Lima et al. 2001), secondary analyses of studies with imipramine, desipramine, and bupropion suggested that depressed cocaine abusers are more likely to show significant reductions in cocaine abuse than nondepressed cocaine abusers (Margolin et al. 1995 Nunes et al. 1991 Ziedonis and Kosten 1991). Furthermore, recent work with desipramine supported its efficacy in opioid-dependent patients, particularly in combination with contingency management therapies (Kosten et al. 2004 Oliveto et al. 1999). 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

The product was evaluated in two multicentre clinical studies that established safety and efficacy. The first (the PRISMS study) was a randomized, double blind placebo-controlled study involving 187 patients. The primary efficacy end-point was the number of clinical relapses recorded. The mean number of relapses over 2 years for the placebo group patients was 2.56, whereas that of the Rebif-treated group was 1.73, a relative reduction of 32 per cent. Rebif treatment also provided positive relative outcomes for several secondary end-points, including the proportion of patients with sustained disability progression. 

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

---