Trial Outcomes & Findings for A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II (NCT NCT04208412)

NCT ID: NCT04208412

Last Updated: 2025-05-02

Results Overview

The primary variable for statistical comparison between treatments in Part 2 of the study was time to use of conventional attack treatment (pdC1INH or rhC1INH intravenous \[iv\] or icatibant) within 12 hours of study drug. Censoring occurs where a subject did not use conventional attack treatment within 12h post-study drug dosing. When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

84 participants

Primary outcome timeframe

12 hours

Results posted on

2025-05-02

Participant Flow

A total of 84 subjects were enrolled, of which 16 were screen failures. The majority of screen failures were due to inclusion criterion not met.

A total of 68 subjects were entered into the open-label safety, tolerability and PK section (Part 1) and subsequently into Part 2, where all 68 subjects were randomized, with 34 subjects randomized to Sequence 1 (600 mg KVD900; Placebo) and 34 subjects randomized to Sequence 2 (Placebo; 600 mg KVD900).

Participant milestones

Participant milestones
Measure	600 mg KVD900, Then Placebo Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.	Placebo, Then 600 mg KVD900 Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Overall Study STARTED	34	34
Overall Study COMPLETED	25	28
Overall Study NOT COMPLETED	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	600 mg KVD900, Then Placebo Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.	Placebo, Then 600 mg KVD900 Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Overall Study Early discontinuation per protocol; sufficient number of subjects completed the study	8	5
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	600 mg KVD900, Then Placebo n=34 Participants Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.	Placebo, Then 600 mg KVD900 n=34 Participants Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Total n=68 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 12.97 • n=5 Participants	35.5 years STANDARD_DEVIATION 13.12 • n=7 Participants	38.3 years STANDARD_DEVIATION 13.23 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	15 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	19 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	33 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Height	1.711 meters STANDARD_DEVIATION 0.0837 • n=5 Participants	1.730 meters STANDARD_DEVIATION 0.1039 • n=7 Participants	1.720 meters STANDARD_DEVIATION 0.0941 • n=5 Participants
Weight	79.89 kg STANDARD_DEVIATION 18.335 • n=5 Participants	82.04 kg STANDARD_DEVIATION 18.865 • n=7 Participants	80.97 kg STANDARD_DEVIATION 18.495 • n=5 Participants
BMI	27.242 kg/m^2 STANDARD_DEVIATION 5.7344 • n=5 Participants	27.336 kg/m^2 STANDARD_DEVIATION 5.2691 • n=7 Participants	27.289 kg/m^2 STANDARD_DEVIATION 5.4656 • n=5 Participants

PRIMARY outcome

Timeframe: 12 hours

Population: A total of 53/68 subjects (77.9%) completed the study. First interquartile values and 95% CI are NA (9.5 to NDA) and 8.0 (3.8 to NA) for the 600 mg KVD900 and Placebo Arm/Groups respectively. Here NA is identical to the footnote.

Outcome measures

Outcome measures
Measure	600 mg KVD900 n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Placebo n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)	NA Time (h) NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics	NA Time (h) NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics

SECONDARY outcome

Timeframe: 12 hours

Population: A total of 53/68 subjects (77.9%) completed the study.

The proportion of participant's HAE attacks to either worsen in attack severity on the PGI-S by one level or more or conventional attack treatment (pdC1INH or rhC1INH intravenous \[iv\] or icatibant) use are listed with censored observations flagged. Frequencies (n, %) of subjects experiencing a worsening on the PGI-S by one level or more or using conventional attack treatment and the number censored are presented. "Y" Row indicates "participants who experienced a worsening in severity, and the "N" Row indicates participants who did not.

Outcome measures

Outcome measures
Measure	600 mg KVD900 n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Placebo n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Proportion of HAE Attacks That Worsen in Severity by One Level or More on the PGI-S or Require Conventional Attack Treatment Within 12 Hours of Study Drug (Full Analysis Set) Y	11 Participants	24 Participants
Proportion of HAE Attacks That Worsen in Severity by One Level or More on the PGI-S or Require Conventional Attack Treatment Within 12 Hours of Study Drug (Full Analysis Set) N	42 Participants	29 Participants

SECONDARY outcome

Timeframe: 12 hours

Population: A total of 53/68 subjects (77.9%) completed the study. First interquartile values and 95% CI are NA (5.9 to NA) and 3.0 (2.0 to 6.0) for the 600 mg KVD900 and Placebo Arm/Groups respectively. Here NA is identical to the footnote.

HAE attack severity assessed using the Patient Global Impression of Severity scale (PGI-S). Censoring occurs where a subject did not worsen in severity or use conventional attack treatment (pdC1INH or rhC1INH intravenous \[iv\] or icatibant) within 12h post-study drug dosing. When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

Outcome measures

Outcome measures
Measure	600 mg KVD900 n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Placebo n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Time to Either Worsening in HAE Attack Severity by One Level or More on the PGI-S or to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)	NA Time (h) NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics	NA Time (h) Interval 6.0 to NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics

SECONDARY outcome

Timeframe: 12 hours

Population: A total of 53/68 subjects (77.9%) completed the study. First interquartile values and 95% CI are 0.6 (0.6 to 1.5) and 2.0 (0.6 to 4.0) for the 600 mg KVD900 and Placebo Arm/Groups respectively. Here NA is identical to the footnote.

Change in HAE attack severity assessed using the Patient Global Impression of Change 7-point transition question (PGI-C). Censoring occurs where an attack rating of "a little better" or higher for two consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing. When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

Outcome measures

Outcome measures
Measure	600 mg KVD900 n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Placebo n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Time to Symptom Relief Defined as HAE Attack Rated as "A Little Better" or Higher on the PGI-C for Two Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)	1.6 Time (h) Interval 1.5 to 3.0	9.0 Time (h) Interval 4.0 to NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics

SECONDARY outcome

Timeframe: 12 hours

Population: A total of 53/68 subjects (77.9%) completed the study. First interquartile values and 95% CI are 2.5 (1.5 to 3.5) and 6.0 (3.0 to NA) for the 600 mg KVD900 and Placebo Arm/Groups respectively. Here NA is identical to the footnote.

The HAE attack symptoms were assessed on a 100 mm visual analogue scale (VAS) ranging from 0 (none) to 100 (very severe). The Composite VAS score is defined as the mean score across all symptoms. Censoring occurs where a ≥50% reduction in Composite VAS Score for three consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing. When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur the event must have occurred \>12 hours following study drug.

Outcome measures

Outcome measures
Measure	600 mg KVD900 n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.	Placebo n=53 Participants In Sequence 1, subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. In Sequence 2, subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Time to Symptom Relief Defined as 50% Reduction in Composite VAS Score for Three Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)	6.0 Time (h) Interval 3.0 to 9.0	NA Time (h) NA represents non-calculable (NC), defined as not enough subjects used conventional attack treatment within 12 hour to complete descriptive statistics

Adverse Events

Part 1: 600 mg KVD900

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 2: 600 mg KVD900

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 2: Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Vice President Clinical

KalVista Pharmaceuticals Ltd.

Phone: 1 (857) 999-0075

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Part 1: 600 mg KVD900 n=68 participants at risk Subjects received a single dose of 600 mg KVD900.	Part 2: 600 mg KVD900 n=58 participants at risk Subjects received a single dose of 600 mg KVD900 to treat eligible HAE attack.	Part 2: Placebo n=55 participants at risk Subjects received a single dose of placebo to treat eligible HAE attack.
Ear and labyrinth disorders Vertigo	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.8% 1/55 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Gastrointestinal disorders Anal incontinence	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.8% 1/55 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Gastrointestinal disorders Dry mouth	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Gastrointestinal disorders Nausea	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	3.4% 2/58 • Number of events 2 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Gastrointestinal disorders Vomiting	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.8% 1/55 • Number of events 2 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
General disorders Malaise	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
General disorders Medical device site rash	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Infections and infestations Cystitis	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Infections and infestations Nasopharyngitis	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	3.6% 2/55 • Number of events 2 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Infections and infestations Urinary tract infection	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Musculoskeletal and connective tissue disorders Back pain	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Nervous system disorders Dizziness	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Nervous system disorders Headache	2.9% 2/68 • Number of events 2 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	5.2% 3/58 • Number of events 3 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.8% 1/55 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Nervous system disorders Tremor	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Skin and subcutaneous tissue disorders Night sweats	1.5% 1/68 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/68 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	1.7% 1/58 • Number of events 1 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)
Vascular disorders Flushing	2.9% 2/68 • Number of events 2 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/58 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)	0.00% 0/55 • Adverse events were collected over the maximum duration of randomized subject participation from screening until final visit (up to 19 weeks). Safety was evaluated for Parts 1 and 2 by the following: * AEs, including serious adverse events (SAEs). * Laboratory test results (clinical chemistry, hematology, coagulation, and urinalysis). * Vital signs (systolic blood pressure \[SBP\], diastolic blood pressure \[DBP\], pulse rate, respiratory rate and body temperature). * Physical exam findings. * ECG results. * Pregnancy test (female subjects of child-bearing potential)