An adverse event (AE) was defined as any unfavourable or unintended disease, or symptom or sign of such a disease, or abnormal laboratory finding that occurred in a patient who received Lipacreon, whether or not considered related to the medicinal product. Also, an AE for which the relationship with Lipacreon could not be ruled out was regarded as an adverse drug reaction (ADR).

1. Related : There is a temporal relationship between the use of the medicinal product and the onset of an AE, or a relapse with readministration,where other factors are less likely to be involved.
2. Relationship cannot be ruled out : There are other potential factors although there is a temporal relationship between the use of the medicinal product and the onset of an AE

It was assessed at 24 weeks after the start of Lipacreon treatment and at the end of the observation period, using the following 4 grades:

Improved, unchanged, exacerbated, unassessable

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed.

It was assessed at 24 weeks after the start of Lipacreon treatment and at the end of the observation period, using the following 4 grades:

Improved, unchanged, exacerbated, unassessable

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed.

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:407 patients, 4 weeks:239 patients, 8 weeks:241 patients, 24 weeks:256 patients, 52weeks: 195 patients).

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:428 patients, 4 weeks:308 patients, 8 weeks:305 patients, 24 weeks:291 patients, 52weeks: 231 patients).

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:429 patients, 4 weeks:319 patients, 8 weeks:316 patients, 24 weeks:309 patients, 52weeks: 235 patients).

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:310 patients, 4 weeks:184 patients, 8 weeks:188 patients, 24 weeks:195 patients, 52weeks: 150 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

PCS8 score is calculated by the following formula (All summed). PCS8 score = (0.23024×SF8GH)+(0.40672×SF8PF)+(0.38317×SF8RP)+(0.33295×SF8BP)+(0.07537×SF8VT)+(-0.01275×SF8SF)+(-0.30469×SF8MH)+(-0.14803×SF8RE)+0.67371

The minimum value of PCS8 is 5.315, and the maximum value is 70.689. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:470 patients, 4 weeks:363 patients, 8 weeks:355 patients, 24 weeks:347 patients, 52weeks: 276 patients).

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:298 patients, 4 weeks:163 patients, 8 weeks:178 patients, 24 weeks:188 patients, 52weeks: 142 patients).

The following nutritional endpoints were measured prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• BMI (height [only prior to the start of Lipacreon treatment] and weight)
• Serum total protein
• Albumin
• Total cholesterol
• Triglycerides
• Haemoglobin

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:465 patients, 4 weeks:331 patients, 8 weeks:333 patients, 24 weeks:328 patients, 52weeks: 246 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

MCS8 score is calculated by the following formula (All summed). MCS8 score = (-0.02020×SF8GH)+(-0.19972×SF8PF)+(-0.16579×SF8RP)+(-0.15992×SF8BP)+(0.16737×SF8VT)+(0.27264×SF8SF)+(0.57583×SF8MH)+(0.42927×SF8RE)+4.34744

The minimum value of MCS8 is 10.108, and the maximum value is 74.511. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8GH scores; 1:63.38, 2:58.54, 3:50.27, 4:40.40, 5:34.38, 6:26.89 The minimum value of SF8GH is 26.89, and the maximum value is 63.38. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8PF scores; 1:53.54, 2:47.77, 3:41.45, 4:27.59, 5:16.69 The minimum value of SF8PF is 16.69, and the maximum value is 53.54. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8RP scores; 1:54.09, 2:47.42, 3:40.65, 4:27.91, 5:21.80. The minimum value of SF8RP is 21.80, and the maximum value is 54.09. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8BP scores; 1:60.35, 2:52.46, 3:46.10, 4:38.21, 5:31.59, 6:21.68. The minimum value of SF8BP is 21.68, and the maximum value is 60.35. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8VT scores; 1:60.01, 2:53.74, 3:44.48, 4:38.51, 5:28.68. The minimum value of SF8VT is 28.68, and the maximum value is 60.01. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8SF scores; 1:55.14, 2:45.60, 3:37.65, 4:29.15, 5:26.00. The minimum value of SF8SF is 26.00, and the maximum value is 55.14. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8MH scores; 1:56.93, 2:50.72, 3:44.94, 4:36.30, 5:27.59. The minimum value of SF8MH is 27.59, and the maximum value is 56.93. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

Baseline, 8 and 24 weeks after the start of treatment, and at the end of the observation period, the patient was asked to fill out the standard SF-8™ (1 month) to assess the patient's QOL, which was recorded in the survey form for this survey. SF-8™:The Medical Outcomes Study 8-Item Short-Form Health Survey (Japanese version). Items are as follows.

Physical health (summary):PCS8, Mental health (summary):MCS8, General health:SF8GH, Physical functioning:SF8PF, Role physical:SF8RP, Body pain:SF8BP, Vitality:SF8VT, Social functioning:SF8SF, Mental health:SF8MH, Role emotional:SF8RE.

SF8RE scores; 1:54.19, 2:48.04, 3:42.24, 4:31.42, 5:19.98. The minimum value of SF8RE is 19.98, and the maximum value is 54.19. Higher scores mean a better outcome.

The means ± SD was calculated by summing the values at each time point.

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:517 patients, 8 weeks:366 patients, 24 weeks:350 patients, 52weeks: 249 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:437 patients, 4 weeks:334 patients, 8 weeks:324 patients, 24 weeks:317 patients, 52weeks: 248 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:483 patients, 4 weeks:376 patients, 8 weeks:365 patients, 24 weeks:358 patients, 52weeks: 285 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:460 patients, 4 weeks:360 patients, 8 weeks:350 patients, 24 weeks:344 patients, 52weeks: 274 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:482 patients, 4 weeks:376 patients, 8 weeks:362 patients, 24 weeks:355 patients, 52weeks: 283 patients).

The following symptoms were assessed as those related to exocrine pancreatic insufficiency prior to the start of Lipacreon treatment, 4, 8 and 24 weeks after the start of treatment, and at the end of the observation period.

• Steatorrhoea (Yes/No)
• Frequency of bowel movements (times/day)
• Diarrhoea (Yes/No)
• Foul stool odour (Yes/No)
• Decreased appetite (Yes/No)
• Abdominal distension (Yes/No)

Among patients in the safety analysis set, 547 patients were included in the efficacy analysis set, excluding 6 patients who were excluded from the efficacy analysis set (Reasons: Unassessable: 5 patients; and off-label use: 1 patient). Among patients in the 547 patients, the patients for which data were obtained at each time frame were analyzed (Baseline:475 patients, 4 weeks:372 patients, 8 weeks:359 patients, 24 weeks:351 patients, 52weeks: 280 patients).