title: Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine.
  
  
  BACKGROUND
  Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N =170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests.
  
  
  RESULTS
  The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥ 4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor.
  
  
  CONCLUSIONS
  The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).
authors: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors: David J
authors: DJ
authors: Hewitt
authors: Vincent
authors: V
authors: Martin
authors: Richard B
authors: RB
authors: Lipton
authors: Jan
authors: J
authors: Brandes
authors: Paulette
authors: P
authors: Ceesay
authors: Regina
authors: R
authors: Gottwald
authors: Eleanor
authors: E
authors: Schaefer
authors: Christopher
authors: C
authors: Lines
authors: Tony W
authors: TW
authors: Ho
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; D018015:Receptors, Calcitonin Gene-Related Peptide; D000082:Acetaminophen; C525458:telcagepant; D007052:Ibuprofen