Trial Outcomes & Findings for OxyNorm Capsules in Post-Operative Pain Study (NCT NCT01675635)

Last Updated: 2018-02-26

Results Overview

To measure resting VAS at 6h(±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bad as you can image at resting stage

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

240 participants

Primary outcome timeframe

Baseline and 6h (±20min)

Results posted on

2018-02-26

Participant Flow

This study is a randomized, double blind, double dummy, multicenter, parallel group, comparative study to compare the efficacy and safety of oxycodone capsule versus morphine tablet. The subject recruited from hospitalized patients poor with moderate to severe pain following surgery. The duration of the study from 2011 Jul to 2011 Dec.

There is no run-in or wash out period involved in this study. On the protocol 240 subjects was planned to be enrolled, but actually 234 subjects was screened and all randomized. Zero screen failure is reasonable for the indication with this study design.

Participant milestones

Participant milestones
Measure	OxyNorm Capsules To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage:l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Overall Study STARTED	117	117
Overall Study COMPLETED	117	117
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

OxyNorm Capsules in Post-Operative Pain Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OxyNorm Capsules n=117 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage:5mg,l0mg and 20mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=117 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 10mg and 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.	Total n=234 Participants Total of all reporting groups
Age, Continuous	43.44 years STANDARD_DEVIATION 11.06 • n=99 Participants	43.29 years STANDARD_DEVIATION 10.53 • n=107 Participants	43.37 years STANDARD_DEVIATION 10.77 • n=206 Participants
Sex: Female, Male Female	101 Participants n=99 Participants	93 Participants n=107 Participants	194 Participants n=206 Participants
Sex: Female, Male Male	16 Participants n=99 Participants	24 Participants n=107 Participants	40 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	116 Participants n=99 Participants	117 Participants n=107 Participants	233 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Region of Enrollment China	117 Participants n=99 Participants	117 Participants n=107 Participants	234 Participants n=206 Participants
Electrocardiogram test normal	88 Participants n=99 Participants	76 Participants n=107 Participants	164 Participants n=206 Participants
Electrocardiogram test abnormal, not clinical significant	29 Participants n=99 Participants	34 Participants n=107 Participants	63 Participants n=206 Participants
Electrocardiogram test abnormal,clinical significant	0 Participants n=99 Participants	5 Participants n=107 Participants	5 Participants n=206 Participants
America Society of Anesthesiologist classification P1(Class I)	61 Participants n=99 Participants	57 Participants n=107 Participants	118 Participants n=206 Participants
America Society of Anesthesiologist classification P2(Class II)	56 Participants n=99 Participants	60 Participants n=107 Participants	116 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and 6h (±20min)

Population: 234 subjects in Full Analysis Set (FAS) in which 4 subjects from each group was excluded for Per Protocol(PP) population, so 113 subjects in PP population in each group for the primary endpoint analysis.

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) baseline of Visual Analogue Scale	46.21 units on a scale Standard Deviation 9.53	45.48 units on a scale Standard Deviation 7.94
Visual Analogue Scale (VAS) in Resting Stage at 6hour (6hour±20 Minutes After Administration of First Dose) 6th hours Visual Analogue Scale	20.21 units on a scale Standard Deviation 15.66	19.94 units on a scale Standard Deviation 15.68

SECONDARY outcome

Timeframe: Baseline,0.5h (±5min), 2h (±10min) and 24h (±20min)

To measure the resting and coughing VAS as 0.5h (±5min), 2h (±10min) and 24h (±20min) after administration of first dose, assessing the intensity of pain and to conduct inter-group comparison

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Resting baseline of Visual Analogue Scale	46.21 units on a scale Standard Deviation 9.53	45.48 units on a scale Standard Deviation 7.96
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Resting visual analogue scale before first dose	46.21 units on a scale Standard Deviation 9.53	45.48 units on a scale Standard Deviation 7.96
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Resting VAS 0.5 hour after first dose	29.87 units on a scale Standard Deviation 13.59	29.80 units on a scale Standard Deviation 12.39
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Resting VAS 2 hours after first dose	20.58 units on a scale Standard Deviation 14.40	20.89 units on a scale Standard Deviation 12.70
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Resting VAS 24 hours after first dose	9.73 units on a scale Standard Deviation 12.52	9.75 units on a scale Standard Deviation 11.19
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Coughing baseline of Visual Analogue Scale	55.16 units on a scale Standard Deviation 12.15	53.91 units on a scale Standard Deviation 10.39
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Coughing visual analogue scale before first dose	55.20 units on a scale Standard Deviation 12.12	53.91 units on a scale Standard Deviation 10.39
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Coughing VAS 0.5 hour after first dose	39.21 units on a scale Standard Deviation 16.56	37.96 units on a scale Standard Deviation 13.61
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Coughing VAS 2hours after first dose	29.68 units on a scale Standard Deviation 17.91	29.30 units on a scale Standard Deviation 13.76
VAS in Both Resting and Coughing Stage at 0.5h, 2h and 24h After Administration of First Dose Coughing VAS 24hours after first dose	17.11 units on a scale Standard Deviation 13.51	16.27 units on a scale Standard Deviation 12.58

SECONDARY outcome

Timeframe: 24 hours after the first dose.

Population: in FAS population

To calculate the subject who used rescue analgesics during the 4 dose interval within the 24-hour observation period and to conduct inter-group comparison

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=117 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=117 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
The Use of Rescue Analgesics During the 24-hour Observation Period First dose interval(0-6h)	7 Participants	5 Participants
The Use of Rescue Analgesics During the 24-hour Observation Period Second dose interval(7-12h)	8 Participants	2 Participants
The Use of Rescue Analgesics During the 24-hour Observation Period Third dose interval(13-18)	1 Participants	0 Participants
The Use of Rescue Analgesics During the 24-hour Observation Period Fourth dose interval(19-24h)	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and 6h (±20min)

To measure coughing VAS at 6h (±20min) after administration of first dose, assessing the intensity of pain, and to conduct inter-group comparison Visual Analogue Scale 0 10 20 30 40 50 60 70 80 90 100 0 means no pain; 100 means pain as bed as you can image applicable for both resting and coughing stage

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) Visual Analogue Scale of baseline coughing	55.16 units on a scale Standard Deviation 12.15	53.91 units on a scale Standard Deviation 10.39
VAS in Coughing Stage at 6h (6h±20min After Administration of First Dose) Visual Analogue Scale after 6hours coughing	28.81 units on a scale Standard Deviation 17.58	28.15 units on a scale Standard Deviation 16.79

SECONDARY outcome

Timeframe: 24 hours after administration of first dose

To assess Sleeping quality assessment during 24 hours after administration of first dose and to conduct inter-group comparison Sleeping quality scale 1. Very Good 2. Good 3. Fair 4. Bad 5. Very Bad

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Sleeping Quality Assessment Very Good	31 Participants	36 Participants
Sleeping Quality Assessment Good	38 Participants	48 Participants
Sleeping Quality Assessment Fair	38 Participants	26 Participants
Sleeping Quality Assessment Bad	5 Participants	2 Participants
Sleeping Quality Assessment Very Bad	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 24 hours after administration of first dose

To assess the Satisfaction with pain control during 24 hours after administration of first dose and to conduct inter-group comparison 1. Very Satisfied 2. Satisfied 3. Fair 4. Not Satisfied 5. Not Satisfied at all

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Satisfaction With Pain Control Fair	19 Participants	12 Participants
Satisfaction With Pain Control Very Satisfied	38 Participants	43 Participants
Satisfaction With Pain Control Satisfied	54 Participants	58 Participants
Satisfaction With Pain Control Not Satisfied	2 Participants	0 Participants
Satisfaction With Pain Control Not Satisfied at all	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24 hours after administration of first dose

To calculate the total amount of study drugs used during the 24 hours and to conduct inter-group comparison The study drug administration is average 6 hours,so the maximal is use 4 times in 24 hours. The investigate to evaluate if the subject need to take the 2nd, 3rd and 4th dose after the mandatory the 1st dose.

Outcome measures

Outcome measures
Measure	OxyNorm Capsules n=113 Participants To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage: l0mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=113 Participants To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Comparison of the Total Amount of Study Drugs Used During the 24 Hours	18.50 mg Standard Deviation 10.37	39.82 mg Standard Deviation 21.79

Adverse Events

OxyNorm Capsules

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Morphine Tablet

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Ms. Dan Zhu, Clinical operation and quality lead of the study

Mundipharma (China) pharmaceutical Co, LTD.

Phone: 0086-10-65636800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OxyNorm Capsules n=117 participants at risk To determine the efficacy and safety of OxyNorm Capsules. OxyNorm Capsules: dosage:5mg,l0mg and 20mg dosage form:capsule frequency:every 6h, duration:24 hours	Morphine Tablet n=117 participants at risk To determine the efficacy and safety of Morphine tablet. Morphine tablet: dosage: 10mg and 20mg; dosage form: tablet; frequency: every 6h; duration: 24 hours.
Gastrointestinal disorders Nausea	12.8% 15/117 • Number of events 15 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	12.0% 14/117 • Number of events 15 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Gastrointestinal disorders Vomiting	6.0% 7/117 • Number of events 7 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	6.0% 7/117 • Number of events 7 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Nervous system disorders Dizziness	6.0% 7/117 • Number of events 7 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	5.1% 6/117 • Number of events 6 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Gastrointestinal disorders abdominal distension	2.6% 3/117 • Number of events 3 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	4.3% 5/117 • Number of events 5 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Musculoskeletal and connective tissue disorders backache	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Infections and infestations postoperative infection	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Nervous system disorders headache	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders serum creatinine increase	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders alanine aminotransferase increase	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Infections and infestations fever	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Vascular disorders hypertension	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Musculoskeletal and connective tissue disorders high tension	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Musculoskeletal and connective tissue disorders muculoskeletalache	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Respiratory, thoracic and mediastinal disorders expectoration	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders anaemia	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Musculoskeletal and connective tissue disorders epigastric pain	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders aspartate aminotransferase increase	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Respiratory, thoracic and mediastinal disorders asthma	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders glycosylated hemoglobin derease	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders blood glucose increase	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	2.6% 3/117 • Number of events 3 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Blood and lymphatic system disorders leucocyte count increase	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Skin and subcutaneous tissue disorders erythema	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Respiratory, thoracic and mediastinal disorders dyspnea	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
General disorders Oropharyngeal pain	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
General disorders chest uncomfortable	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
Renal and urinary disorders blood urea increase	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	1.7% 2/117 • Number of events 2 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.
General disorders swelling	0.00% 0/117 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.	0.85% 1/117 • Number of events 1 • The protocol requires safety follow up until 24 hours after the last study medication dosing. So the longest time one subject in the study is 48 hours after the 1st study medication doing, include taking full of the 4 times dosing(intotal 24 hours) following by safety follow up for 24 hours.