No abstract

1. Eight hundred and forty‐six patients with pain in one or two joints of the hip, knee, ankle or wrist participated in a randomised double‐ blind trial to compare the efficacy, tolerability and effect on quality of life of diclofenac sodium slow release (DSR) 100 mg daily and a combination of dextropropoxyphene 180 mg and paracetamol 1.95 g daily (D&P). Health status or quality of life was measured using the Nottingham Health Profile (NHP) questionnaire. 2. Pain as measured by a visual analogue scale (VAS) showed 8% greater pain reduction with DSR as compared with D&P (P less than 0.05). Physical mobility as measured by the NHP improved by 13% more with DSR as compared with D&P (P less than 0.01). Energy, sleep, social isolation and emotional reactions did not differ significantly between the two treatment groups, but both treatment groups showed improvement during the trial. More D&P patients as compared with DSR patients reported problems with their job of work (P less than 0.05), and time lost from work (P less than 0.05). 3. Patients on D&P suffered an excess of tiredness or sleep disturbance (50 vs 21, P less than 0.01) whilst patients treated with DSR had an excess of abdominal or epigastric pain or indigestion (40 vs 18, P less than 0.01). 57 patients were withdrawn from DSR and 65 from D&P.

No abstract

Dalcetrapib targets cholesteryl ester transfer protein and increases high-density lipoprotein cholesterol (HDL-C) levels. It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins. Three crossover studies in healthy males investigated the pharmacokinetic drug-drug interaction potential of 900 mg dalcetrapib and statins: two 3-period studies (dalcetrapib plus pravastatin or rosuvastatin) and a 2-period study (dalcetrapib plus simvastatin). Effect on lipids and safety were secondary end points. The 900 mg dose investigated is higher than the 600 mg dose currently being investigated in Phase III. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin was not associated with significant increases in statin exposure except for a 26% increase in rosuvastatin C(max) (90% CI 1.088 to 1.468) but not AUC(0-24) (90% CI 0.931 to 1.085). Dalcetrapib AUC(0-24) and C(max) were not significantly altered by coadministration with pravastatin, and were significantly lower when dalcetrapib was coadministered with rosuvastatin or simvastatin compared with dalcetrapib alone. The HDL-C increase with dalcetrapib was not compromised by coadministration with statins, and reduction in low-density lipoprotein cholesterol with dalcetrapib coadministered with statins was greater than with statins alone. Dalcetrapib alone and coadministered with statins was generally well tolerated.

These results indicate no clinically relevant interactions for co-administration of dalcetrapib with atorvastatin.