A placebo-controlled study to investigate the efficacy of a combination analgesic treatment compared to its individual components in primary dysmenorrhoea.

INTERVENTION: Trade Name: Panadol Extra Tablets Product Name: Panadol Extra Tablets Product Code: Not applicable Pharmaceutical Form: Coated tablet INN or Proposed INN: Paracetamol Other descriptive name: acetaminophen Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ INN or Proposed INN: Caffeine Other descriptive name: Anhydrous caffeine Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 65‐ Pharmaceutical form of the placebo: Coated tablet Route of administration of the placebo: Oral use Trade Name: Panadol Tablets Product Name: Panadol Tablets Product Code: Not applicable Pharmaceutical Form: Coated tablet INN or Proposed INN: Paracetamol Other descriptive name: Acetaminophen Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Product Name: Caffeine Product Code: Not applicable Pharmaceutical Form: Coated tablet INN or Proposed INN: Caffeine Other descriptive name: anhydrous caffeine Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 65‐ CONDITION: primary dysmenorrhoea ; MedDRA version: 7.1 Classification code 10013935 PRIMARY OUTCOME: Main Objective: Main objective : To compare the efficacy of a single dose of paracetamol and caffeine with a single dose of paracetamol alone for pain relief in patients with primary dysmenorrhoea symptoms.; To compare the efficacy of a single dose of paracetamol and caffeine with a single dose of caffeine alone for pain relief in patients with primary dysmenorrhoea symptoms; Primary end point(s): Primary endpoint:; TOTPAR0‐2 hours for pain relief.; TOTPAR0‐2 hours will be generated for each patient by summing the pain relief scores of none (0), a little (1), some (2), a lot (3) and complete (4) over the time points from 0 to 2 hours, weighting for the nominal time between time points.; Secondary Objective: •To compare the efficacy of a single dose of paracetamol and caffeine with a single dose of paracetamol alone for abdominal cramping, backache and tiredness in patients with primary dysmenorrhoea symptoms.; •To compare the efficacy of a single dose of paracetamol and caffeine with a single dose of caffeine alone for abdominal cramping, backache and tiredness in patients with primary dysmenorrhoea symptoms.; •To compare the efficacy of a single dose of paracetamol and caffeine with a single dose of placebo for pain relief, abdominal cramping, backache and tiredness in patients with primary dysmenorrhoea symptoms.; •To compare the efficacy of a single dose of paracetamol alone with a single dose of placebo for pain relief, abdominal cramping, backache and tiredness in patients with primary dysmenorrhoea symptoms.; •To assess the safety (adverse events) of a single dose of Panadol Extra Tablets (1000 mg/130 mg), Panadol Tablets (1000 mg), caffeine tablet (130 mg) and placebo tablet.; INCLUSION CRITERIA: • Female subjects aged 18 years upwards. Self‐reported history of Grade 2 or 3 (Andersch and Milsom scoring system – Am J Obstet Gynecol 1982; 144:655‐660) primary dysmenorrhoea. ? Grade 0 = menstruation is not painful, and daily activity is unaffected. OTC analgesics are not required. ? Grade 1 = menstruation is painful but seldom inhibits normal activity; OTC analgesics are seldom required; mild pain. ? Grade 2 = daily activity unaffected; OTC analgesics required and give sufficient relief so that absence from college or work is unusual; moderate pain ? Grade 3 = Activity clearly inhibited; poor effect of analgesics; vegetative symptoms (eg. headache, fatigue, nausea, backache); severe pain • At least 3 painful menstrual cycles during the previous 4 months which have required medication with OTC analgesics. • Duration of menstrual cycle within the range 21‐35 days. Onset of dysmenorrhoea < 3 years after menarche. Patient known, b