Trial Outcomes & Findings for A Study to Compare Methodologies for Assessing Glucose-Dependent Insulin Secretion (0000-104)(COMPLETED) (NCT NCT00782418)

Last Updated: 2016-12-21

Results Overview

Comparison of Glucose Dependent Insulin Secretion (GDIS) measured after HGC at steady-state to GDIS measured after GGI at the highest glucose infusion rate. Insulin Secretion Rate (ISR)/ Blood Glucose (BG)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose

Results posted on

2016-12-21

Participant Flow

First Patient Entered: 19-Sep-2008 Last Patient, Last Visit: 05-Mar-2009 1 site

Inclusion criteria: Subjects with a Body Mass Index (BMI) of ≤26 kg/m2 Exclusion criteria: History of diabetes or family history of diabetes. Subjects on a carbohydrate restricted diet. An amendment added 8 subjects to go before study completion and instituted down dosing for subjects assigned to exenatide 5 μg in the HGC period to placebo

Participant milestones

Participant milestones
Measure	HGC - Exenatide 5 μg Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo Hyperglycemic Clamp: Treatment Group Placebo	Exenatide 5 ug Down Dosed to Placebo (HGC) Hyperglycemic Clamp: Treatment Group Exenatide 5 ug down dosed to placebo	GGI - Exenatide 5 μg Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	Placebo (HGC or GGI) Hyperglycemic Clamp or Graded Glucose Infusion: Treatment Group Placebo
Period 1 Procedure/Treatment Groups STARTED	3	4	4	2	5	5	4
Period 1 Procedure/Treatment Groups COMPLETED	1	4	4	2	4	4	4
Period 1 Procedure/Treatment Groups NOT COMPLETED	2	0	0	0	1	1	0
Period 2 Procedure/Treatment Groups STARTED	3	4	4	1	3	4	4
Period 2 Procedure/Treatment Groups COMPLETED	3	4	4	1	3	4	4
Period 2 Procedure/Treatment Groups NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	HGC - Exenatide 5 μg Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo Hyperglycemic Clamp: Treatment Group Placebo	Exenatide 5 ug Down Dosed to Placebo (HGC) Hyperglycemic Clamp: Treatment Group Exenatide 5 ug down dosed to placebo	GGI - Exenatide 5 μg Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	Placebo (HGC or GGI) Hyperglycemic Clamp or Graded Glucose Infusion: Treatment Group Placebo
Period 1 Procedure/Treatment Groups Adverse Event	1	0	0	0	0	0	0
Period 1 Procedure/Treatment Groups Study placed on temporary hold	1	0	0	0	1	1	0

Baseline Characteristics

A Study to Compare Methodologies for Assessing Glucose-Dependent Insulin Secretion (0000-104)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Patients n=27 Participants All patients from all arms
Age, Continuous	29.3 years STANDARD_DEVIATION 9.1 • n=5 Participants
Gender Female	0 Participants n=5 Participants
Gender Male	27 Participants n=5 Participants
Body Mass Index	23.3 kg/m^2 STANDARD_DEVIATION 2.1 • n=5 Participants

PRIMARY outcome

Timeframe: Steady-state of HGC: 90 - 120 minutes post dose; highest glucose infusion rate of GGI: 120 - 160 minutes post dose

Population: All subjects treated

Outcome measures

Outcome measures
Measure	HGC - Exenatide 5 μg n=6 Participants Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg n=8 Participants Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo n=11 Participants Hyperglycemic Clamp: Treatment Group Placebo	GGI - Exenatide 5 μg n=6 Participants Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg n=9 Participants Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	GGI - Placebo n=8 Participants Graded Glucose Infusion: Treatment Group Placebo
Change From Baseline in Insulin Secretion Rate (ISR) Normalized to Ambient Plasma Glucose	2.14 (ng/min) / (mg/dL) Interval 1.52 to 2.52	1.49 (ng/min) / (mg/dL) Interval 0.78 to 2.16	0.53 (ng/min) / (mg/dL) Interval 0.19 to 0.73	2.95 (ng/min) / (mg/dL) Interval 0.94 to 3.88	2.07 (ng/min) / (mg/dL) Interval 0.82 to 3.3	0.71 (ng/min) / (mg/dL) Interval 0.1 to 1.22

PRIMARY outcome

Timeframe: Pre and Post glucose infusion

Population: All subjects treated

Outcome measures

Outcome measures
Measure	HGC - Exenatide 5 μg n=6 Participants Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg n=8 Participants Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo n=11 Participants Hyperglycemic Clamp: Treatment Group Placebo	GGI - Exenatide 5 μg Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	GGI - Placebo Graded Glucose Infusion: Treatment Group Placebo
Change From Baseline in C-peptide Concentration	29.3 ng/mL Interval 25.2 to 35.1	22.6 ng/mL Interval 14.0 to 34.1	6.24 ng/mL Interval 2.3 to 8.9	—	—	—

PRIMARY outcome

Timeframe: Pre and Post glucose infusion

Population: All subjects treated

Outcome measures

Outcome measures
Measure	HGC - Exenatide 5 μg n=6 Participants Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg n=8 Participants Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo n=11 Participants Hyperglycemic Clamp: Treatment Group Placebo	GGI - Exenatide 5 μg Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	GGI - Placebo Graded Glucose Infusion: Treatment Group Placebo
Change From Baseline in Insulin Concentration	592 μIU(insulin)/mL Interval 445.0 to 695.0	293 μIU(insulin)/mL Interval 128.0 to 597.0	46.5 μIU(insulin)/mL Interval 16.2 to 123.0	—	—	—

Adverse Events

HGC - Exenatide 5 μg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

HGC - Exenatide 1.5 μg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

HGC - Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

GGI - Exenatide 5 μg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

GGI - Exenatide 1.5 μg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GGI - Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HGC - Exenatide 5 μg n=9 participants at risk Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg n=9 participants at risk Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo n=10 participants at risk Hyperglycemic Clamp: Treatment Group Placebo	GGI - Exenatide 5 μg n=7 participants at risk Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg n=8 participants at risk Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	GGI - Placebo n=11 participants at risk Graded Glucose Infusion: Treatment Group Placebo
Gastrointestinal disorders Vomiting	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.

Other adverse events

Other adverse events
Measure	HGC - Exenatide 5 μg n=9 participants at risk Hyperglycemic Clamp (HGC): Treatment Group Exenatide 5 μg	HGC - Exenatide 1.5 μg n=9 participants at risk Hyperglycemic Clamp: Treatment Group Exenatide 1.5 μg	HGC - Placebo n=10 participants at risk Hyperglycemic Clamp: Treatment Group Placebo	GGI - Exenatide 5 μg n=7 participants at risk Graded Glucose Infusion (GGI): Treatment Group Exenatide 5 μg	GGI - Exenatide 1.5 μg n=8 participants at risk Graded Glucose Infusion: Treatment Group Exenatide 1.5 μg	GGI - Placebo n=11 participants at risk Graded Glucose Infusion: Treatment Group Placebo
Ear and labyrinth disorders Vertigo	22.2% 2/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	28.6% 2/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	9.1% 1/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Abdominal Pain Upper	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Diarrhoea	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Nausea	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	20.0% 2/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	71.4% 5/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Retching	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Gastrointestinal disorders Vomiting	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	20.0% 2/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	42.9% 3/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
General disorders Asthenia	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
General disorders Fatigue	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	10.0% 1/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	12.5% 1/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Infections and infestations Tooth Abscess	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Investigations Blood Phosphorus Decreased	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Disturbance In Attention	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Dizziness	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Headache	22.2% 2/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	22.2% 2/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	10.0% 1/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	37.5% 3/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	9.1% 1/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Presyncope	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	28.6% 2/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Nervous system disorders Syncope	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Respiratory, thoracic and mediastinal disorders Sneezing	11.1% 1/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Skin and subcutaneous tissue disorders Rash Papular	22.2% 2/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	14.3% 1/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	9.1% 1/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.
Skin and subcutaneous tissue disorders Thrombophlebitis Superficial	22.2% 2/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/9 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/10 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/7 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/8 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.	0.00% 0/11 • Adverse experiences were collected from the time the consent is signed through the 14 day follow up period after all treatment periods were completed. AE s were assessed by clinical evaluation including vital signs, physical examination, medical history, clinical laboratory safety assessment (hematology, chemistry, urinalysis), and ECG at timepoints specified in the study. Subjects were queried at each visit for any adverse experiences since the previous visit.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER