Fentanyl

Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted.

Questionnaire of opioid withdrawal symptoms is a clinician rated 11-item scale that primarily evaluates the physical components of opioid withdrawal and is based on questions and clinical observations. The total score of questionnaire of opioid withdrawal symptoms is the sum of all individual items, with less than (\<) 5 points = no withdrawal, 5 to 12 points = mild withdrawal, 13 to 24 points = moderate withdrawal, 25 to 36 points = moderately severe withdrawal and greater than (\>) 36 points = severe withdrawal.

The DQ is a clinician rated 5-item scale that evaluates dependence on drug and based on questions (Q). Based on participant's answer to Q in questionnaire, Investigator assessed whether drug dependence occurred. It comprises 5 Q which are: continuing drug for reason other than pain, using drug in more dosage than prescribed to have effect other than treatment of pain, have ever used drug with more dosage than prescribed for other purpose, anxiety with the thought of stopping drug for reason other than aggravation of symptoms by stopping this drug and feeling to violate law to get this drug.

Pain visual analog scale was used to assess the amount of pain experienced by the participant throughout the day by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from "no pain (0 mm)" to "worst possible pain (100 mm)".

Pain intensity was measured by assessing the average intensity of pain experienced by the participant in daily living throughout the day by 4 grades: no pain at all, mild (slightly painful, but not worried), moderate (painful, but bearable) and severe (painful and unbearable).

The participants assessed total painful time in 1 day by the following 5 grades: less than 4 hours, 4 hours to less than 8 hours, 8 hours to less than 12 hours, 12 hours or more and all day.

The quality of sleep was assessed by participants that how well they have slept from the previous assessment to current assessment time by the following 4 grades: can sleep well, can sleep moderately well, cannot sleep much and cannot sleep at all.

Rescue treatment was used for participants with lack of analgesic efficacy, to have relief from breakthrough pain and in cases where withdrawal symptoms occur. The reference one-time rescue dose used was oral morphine 5 milligram (mg) for the investigational product fentanyl one-day transdermal patch 12.5 mcg per hr. The number of rescue treatments per day were reported.

The SF-36 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.

The treating physician assessed the therapeutic efficacy of the treatment by 2 grades: effective and ineffective. Numbers of participants with effective and ineffective therapeutic efficacy with the treatment were reported.

The participants assessed their satisfaction with therapeutic efficacy by 5 grades: satisfied very much, satisfied, equivocal, dissatisfied and dissatisfied very much. Percentage of participants who were at least satisfied (satisfied, satisfied very much) or at least neither satisfied nor dissatisfied (dissatisfied, dissatisfied very much) were reported.

The BPI-SF is a self-report questionnaire designed to assess the severity and impact of pain on daily functions. It includes pain interference score which is mean value for scores for 9 BPI-SF questions ranging between 0 (does not interfere) to 10 (completely interferes) and pain subscale score which is mean value for scores for BPI-SF questions 3 to 6 ranging between 0 (no pain) to 10 (pain as bad as can imagine). Total BPI-SF score is an average of pain interference score and pain subscale score and ranges from 0 to 10; higher score indicates more pain or pain interference.

Pain control was assessed based on change in Visual Analog Scale (VAS) and number of daily rescue doses during 3 days before completion of study drug from 3 days before start of study drug. For VAS score, a difference of less than or equal to +15 millimeter (mm) and for rescue doses, a difference of less than or equal to 1 was considered significant to achieve pain control. Pain Intensity VAS ranged from 0 mm (no pain) to 100 mm (severest pain conceivable) and rescue dose was defined as dose of fast-acting opioid analgesic (except fentanyl preparations) used for lack of analgesic effect.

The Cmax is the maximum observed plasma concentration of Fentanyl.

The Tmax is the time to reach the maximum observed plasma concentration of Fentanyl.

The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.

The AUC (0-infinity) is the area under the plasma Fentanyl concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Fentanyl concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.

Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).