Trial Outcomes & Findings for Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers (NCT NCT01128192)

NCT ID: NCT01128192

Last Updated: 2014-12-25

Results Overview

Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

-30 min and -15 min on Day 2 and Day 9

Results posted on

2014-12-25

Participant Flow

Participants were healthy men aged 18-50 years with a body mass index (BMI) ≤25 kg/m2 who came to the VA San Diego Healthcare System Metabolic Research medical clinic. Recruitment occurred between August of 2009 until March 2010.

Participants were excluded if they had a family history of diabetes or a baseline diagnosis of impaired glucose tolerance.

Participant milestones

Participant milestones
Measure	Pasireotide 600 μg sc Bid 19 healthy male volunteers were randomized to receive Pasireotide 600 μg (n=19). All participants completed the study.	Pasireotide 900 μg sc Bid 19 healthy male volunteers were randomized to receive Pasireotide 900 μg (n=19). All participants completed the study.	Pasireotide 1200 μg sc Bid 7 healthy male volunteers were randomized to receive Pasireotide 1200 μg (n=7). This arm was used in safety analysis only.
Overall Study STARTED	19	19	7
Overall Study COMPLETED	19	19	7
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Somatostatin Analogue SOM230 (Pasireotide) in Healthy Male Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pasireotide 600 μg sc Bid n=19 Participants Pasireotide 600 μg sc bid n=19	Pasireotide 900 μg sc Bid n=19 Participants Pasireotide 900 μg sc bid n=19	Total n=38 Participants Total of all reporting groups
Age, Continuous	24.3 years STANDARD_DEVIATION 4.6 • n=5 Participants	24.6 years STANDARD_DEVIATION 6.1 • n=7 Participants	24.45 years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Body Mass Index BMI (kg/m2)	23.30 kg/m2 STANDARD_DEVIATION 1.61 • n=5 Participants	23.68 kg/m2 STANDARD_DEVIATION 2.04 • n=7 Participants	23.49 kg/m2 STANDARD_DEVIATION 1.85 • n=5 Participants
Weight (kg)	75.67 kg STANDARD_DEVIATION 8.11 • n=5 Participants	74.49 kg STANDARD_DEVIATION 8.41 • n=7 Participants	75.08 kg STANDARD_DEVIATION 8.26 • n=5 Participants

PRIMARY outcome

Timeframe: -30 min and -15 min on Day 2 and Day 9

Change from Day 2 and Day 9 of insulin basal levels (2-step hyperglycemic clamp test with arginine stimulation)

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Insulin Basal Level	-24.37 pmol/L Standard Deviation 10.42	-29.60 pmol/L Standard Deviation 16.05

PRIMARY outcome

Timeframe: 0-10 mins, 10-180 mins, 0-180 mins (Day 2 and Day 9)

Blood samples were taken at -30 min, -15 min, 0 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min, 105 min, 120 min, 135 min, 150 min, 165 min, 180 min to assess the plasma insulin levels during Hyperglycemic Clamp (2-step hyperglycemic clamp test with arginine stimulation). The mean change in plasma insulin levels from Day 2 to Day 9 were calculated as Values on Day 9 - Values on Day 2.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp AUC 0-10 min	-28.07 h*pmol/L Standard Deviation 19.15	-27.95 h*pmol/L Standard Deviation 18.56
Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp AUC 10-180 min	-1450.59 h*pmol/L Standard Deviation 1237.44	-1474.65 h*pmol/L Standard Deviation 1009.00
Change in Area Under the Curve (AUC) of Plasma Insulin Level 0-10mins, 10-180mins, 0-180mins During Hyperglycemic Clamp AUC 0-180 min	-1478.65 h*pmol/L Standard Deviation 1254.66	-1502.60 h*pmol/L Standard Deviation 1022.33

PRIMARY outcome

Timeframe: Day 3 and Day 10

Change from Day 3 and Day 10 of Basal EGP (Hyperinsulinemic-Euglycemic Clamp)

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Basal Endogenous Glucose Production (EGP)	-0.041 mg/kg/min Standard Deviation 0.342	0.112 mg/kg/min Standard Deviation 0.308

PRIMARY outcome

Timeframe: Day 3 and Day 10

Change from Day 3 and Day 10 of low dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Low Dose % Endogenous Glucose Production (EGP) Inhibition	-7.54 percentage of EGP Inhibition Standard Deviation 23.47	-6.28 percentage of EGP Inhibition Standard Deviation 16.31

PRIMARY outcome

Timeframe: Day 3 and Day 10

Change from Day 3 and Day 10 of high dose % EGP Inhibition (Hyperinsulinemic-Euglycemic Clamp)

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in High Dose % Endogenous Glucose Production (EGP) Inhibition	-2.06 percentage of EGP inhibition Standard Deviation 15.65	0.00 percentage of EGP inhibition Standard Deviation 0.00

PRIMARY outcome

Timeframe: Day 3 and Day 10

Change from Day 3 and Day 10 in Low-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Low-Dose Glucose Disposal Rate (GDR)	-0.029 mg/kg/min Standard Deviation 2.230	0.791 mg/kg/min Standard Deviation 2.144

PRIMARY outcome

Timeframe: Day 3 and Day 10

Change from Day 3 and Day 10 in High-Dose Glucose Disposal Rate (GDR) during Hyperinsulinemic-Euglycemic Clamp.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=19 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in High-Dose Glucose Disposal Rate (GDR)	0.004 mg/kg/min Standard Deviation 2.051	-0.027 mg/kg/min Standard Deviation 2.099

SECONDARY outcome

Timeframe: -30 minutes on Day 1 and -30 minutes on Day 8

An Oral Glucose Tolerance Test was performed at Day 1 (baseline) and Day 8 (post-treatment). Samples were taken at -30 min to assess the fasting plasma glucose level. The mean change in fasting plasma glucose level from Day 1 to Day 8 was assessed.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=18 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Fasting Plasma Glucose Level	-0.10 mmol/L Standard Deviation 0.36	0.12 mmol/L Standard Deviation 0.50

SECONDARY outcome

Timeframe: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)

Blood samples were taken at -30 min, 0 min, 30 min, 60 min, 90 min, 120 min, 150 min, 180 min to assess the plasma glucose level. The mean change in plasma glucose level from Day 1 to Day 8 were calculated as Values on Day 8 - Values on Day 1.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=18 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 0-30 min	-0.43 h*mmol/L Standard Deviation 0.43	-0.86 h*mmol/L Standard Deviation 0.45
Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 30-180 min	14.72 h*mmol/L Standard Deviation 4.23	12.35 h*mmol/L Standard Deviation 4.25
Change in Area Under the Curve (AUC) of Plasma Glucose 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 0-180 min	14.29 h*mmol/L Standard Deviation 4.02	11.49 h*mmol/L Standard Deviation 4.49

SECONDARY outcome

Timeframe: -30 minutes on Day 1 and -30 minutes on Day 8

An Oral Glucose Tolerance Test was performed at Day 1 (baseline) and Day 8 (post-treatment). Samples were taken at -30 min to assess the fasting plasma insulin level. The mean change in fasting plasma insulin level from Day 1 to Day 8 was assessed.

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=18 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change Fasting Plasma Insulin Level	-6.62 pmol/L Standard Deviation 11.17	-11.69 pmol/L Standard Deviation 10.96

SECONDARY outcome

Timeframe: 0-30 mins, 30-180 mins, 0-180 mins (Day 1 and Day 8)

Blood samples were taken at -30 min, 0 min, 30 min, 60 min, 90 min, 120 min, 150 min, 180 min to assess the plasma insulin level. The mean change in plasma insulin level from Day 1 to Day 8 were calculated as Values on Day 8 - Values on Day 1

Outcome measures

Outcome measures
Measure	Pasireotide 600 µg sc Bid n=19 Participants Pasireotide 600 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.	Pasireotide 900 µg sc Bid n=18 Participants Pasireotide 900 µg was injected subcutaneously twice daily from Day 3-10. Baseline OGTT was conducted on Day 1 (pre-treatment) and a post-treatment OGTT was conducted on Day 8.
Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 0-30 min	-104.18 h*pmol/L Standard Deviation 90.60	-100.90 h*pmol/L Standard Deviation 68.99
Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 30-180 min	-184.96 h*pmol/L Standard Deviation 126.57	-262.15 h*pmol/L Standard Deviation 158.58
Change in Area Under the Curve (AUC) of Plasma Insulin 0-30mins, 30-180mins, 0-180mins During Oral Glucose Tolerance Test (OGTT) AUC 0-180 min	-289.14 h*pmol/L Standard Deviation 162.54	-363.06 h*pmol/L Standard Deviation 191.58

Adverse Events

Pasireotide 600 μg sc Bid

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Pasireotide 900 μg sc Bid

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Pasireotide 1200 μg sc Bid

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Principal Investigator

Veterans Medical Research Foundation

Phone: 858-552-8585

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Pasireotide 600 μg sc Bid n=19 participants at risk Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.	Pasireotide 900 μg sc Bid n=19 participants at risk Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.	Pasireotide 1200 μg sc Bid n=7 participants at risk Forty-five healthy male volunteers were randomized to receive pasireotide 600 μg (n=19), 900 μg (n=19) or 1200 μg (n=7) sc bid. All participants completed the study. Due to an increased severity of gastrointestinal AEs in the 1200 μg bid arm, randomization to this dose was discontinued after seven participants had completed the 7 days of treatment. These participants were included in the safety analyses only.
Gastrointestinal disorders Nausea	52.6% 10/19 • Number of events 10 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	52.6% 10/19 • Number of events 10 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	71.4% 5/7 • Number of events 5 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Abdominal Cramping	31.6% 6/19 • Number of events 6 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	47.4% 9/19 • Number of events 9 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	57.1% 4/7 • Number of events 4 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Loose Stools (soft stools)	26.3% 5/19 • Number of events 5 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	68.4% 13/19 • Number of events 13 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	28.6% 2/7 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Burning Sensation	21.1% 4/19 • Number of events 4 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Diarrhea	15.8% 3/19 • Number of events 3 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	21.1% 4/19 • Number of events 4 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	14.3% 1/7 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Fatigue	15.8% 3/19 • Number of events 3 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	14.3% 1/7 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Vomiting/emesis	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	15.8% 3/19 • Number of events 3 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	42.9% 3/7 • Number of events 3 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Gas (Flatulence)	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	21.1% 4/19 • Number of events 4 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Skin and subcutaneous tissue disorders Injection site redness	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Skin and subcutaneous tissue disorders Injection site stinging	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection (common cold)	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	15.8% 3/19 • Number of events 3 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Frequent Stools	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Impacted wisdom tooth	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Light colored stool	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Pressure in gut	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Stomach ache	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Stomach cramps	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Stomach fullness	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Gastrointestinal disorders Heartburn	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Skin and subcutaneous tissue disorders Injection site bruise	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Sleepiness	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Dizziness	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	14.3% 1/7 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Histamine-like reaction	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	14.3% 1/7 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Sweating	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	14.3% 1/7 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
General disorders Vasovagal reaction while voiding	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	10.5% 2/19 • Number of events 2 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.
Injury, poisoning and procedural complications Infiltration, left ACFf	0.00% 0/19 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	5.3% 1/19 • Number of events 1 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.	0.00% 0/7 • Adverse events (AE) were collected in real time as reported by each study subject. The study Investigators' reviewed and evaluated each individually reported Adverse Event within one week of reporting (if not immediately upon report). The investigator provided a listing of each subject's AEs. The individual AEs that occurred in each subject were then identified using the Investigator's term and AE frequency was summarized by dose group and adverse event.