APeX-J: Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan

• Sponsor: BioCryst Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03873116
• Collaborator: (none)
• Enrollment: 19
• Locations: 10
• Arms: 3
• Anticipated Duration (Months): 27.1
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase 3, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II HAE who live in Japan.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Angioedema, HAE	Drug: BCX7353 capsules; Drug: BCX7353 capsules; Drug: Placebo oral capsule	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX7353 as an Oral Treatment for the Prevention of Attacks in Subjects With Hereditary Angioedema
• Actual Study Start Date: Feb 28, 2019
• Actual Primary Completion Date: Nov 15, 2019
• Anticipated Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BCX7353 110mg once daily BCX7353 capsules administered orally once daily	Drug: BCX7353 capsules; BCX7353 capsules administered orally once daily
Experimental: BCX7353 150mg once daily BCX7353 capsules administered orally once daily	Drug: BCX7353 capsules; BCX7353 capsules administered orally once daily
Placebo Comparator: Placebo Matching placebo oral capsules administered orally once daily	Drug: Placebo oral capsule; Matching placebo capsules administered orally once daily

Outcome Measures

Primary Outcome Measures

1. Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168) [24 weeks]

   The angioedema event rate and the treatment comparisons between each berotralstat dose and placebo in the rate of expert-confirmed angioedema events during the entire dosing period was analyzed using a negative binomial regression model. The number of expert-confirmed angioedema events was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline monthly angioedema event rate) and study (for the combined study analysis) were included as covariates, and the logarithm of duration on treatment was included as an offset variable. The estimated rate of angioedema events for each treatment group, the treatment differences expressed as the angioedema event rate ratio (berotralstat) over placebo rate ratio), and their associated 95% confidence intervals (CIs) were provided from the negative binomial regression model.

Secondary Outcome Measures

1. Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks. [24 weeks]

   Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1.

2. Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period [Day 8 through to 24 weeks]

   The rate of expert-confirmed angioedema events for the effective treatment period gives an analysis of the efficacy of active treatment after berotralstat had reached steady-state concentrations, given the effective half-life of 150 mg berotralstat in Study BCX7353-106 (Study 106) of 89 hours.

3. Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score) [Baseline and 24 weeks]

   Change in Quality of Life, on a 1-100 scale, where higher scores indicate more impairment and a decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL is only validated for adults; however, data were collected on all adult and adolescent study subjects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• A clinical diagnosis of hereditary angioedema (HAE) Type 1 or Type 2, defined as having a C1-INH functional level and a C4 level below the lower limit of the normal (LLN) reference range, as assessed during the Screening period.

• Access to and ability to use one or more acute medications approved by the relevant competent authority for the treatment of acute attacks of HAE

• Subjects must be medically appropriate for on-demand treatment as the sole medicinal management for their HAE during the study.

• Subjects must have a specified number of expert-confirmed attacks during the run-in period of 56 days from the Screening visit.

• Acceptable effective contraception

• Written informed consent

Key Exclusion Criteria:

• Pregnancy or breast-feeding

• Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study

• Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study

• Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology

• Use of C1-INH within 14 days or use of androgens or tranexamic acid within 28 days prior to the Screening visit for prophylaxis of HAE attacks, or initiation of these drugs during the study

• Current participation in any other investigational drug study or received another investigational drug within 30 days of the Screening visit

• Prior enrollment in a BCX7353 study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site	Chiba		Japan
2	Study Site	Gunma		Japan
3	Study Site	Hokkaido		Japan
4	Study Site	Nagoya		Japan
5	Study Site	Osaka		Japan
6	Study Center	Saga		Japan
7	Study Site	Saitama		Japan
8	Study Site	Shimane		Japan
9	Study Site	Shizuoka		Japan
10	Study Site	Tokyo		Japan

Sponsors and Collaborators

• BioCryst Pharmaceuticals

Investigators

• Principal Investigator: Isao Ohsawa, Saiyu Soka Hospital

Study Documents (Full-Text)

• Study Protocol - Aug 7, 2020
• Statistical Analysis Plan - Nov 4, 2019

More Information

Publications

None provided.

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03873116
• Other Study ID Numbers: BCX7353-301
• First Posted: Mar 13, 2019
• Last Update Posted: Mar 4, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by BioCryst Pharmaceuticals: BCX7353
• Additional relevant MeSH terms: Angioedema; Angioedemas, Hereditary; Berotralstat

Study Results

Participant Flow

Pre-assignment Detail

Subjects with HAE Type 1 or Type 2 were eligible for the study following assessment of data obtained from screening procedures, including demonstration of a minimum number of qualifying angioedema events documented during a prospective run-in period of 56 days from the date of the screening visit. Randomization was stratified by the angioedema event rate over the period between screening and randomization (≥ 2 angioedema events per month vs. < 2 angioedema events per month).

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.
Period Title: Overall Study
STARTED	6	7	6
COMPLETED	6	7	5
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo	Total
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.	Total of all reporting groups
Overall Participants	6	7	6	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (15.03)	37.3 (9.05)	42.3 (13.52)	42.1 (12.61)
Sex: Female, Male (Count of Participants)
Female	5 83.3%	6 85.7%	5 83.3%	16 84.2%
Male	1 16.7%	1 14.3%	1 16.7%	3 15.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	6 100%	6 85.7%	6 100%	18 94.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 14.3%	0 0%	1 5.3%
Baseline expert-confirmed angioedema event rate (participants) [Number]
≥ 2 events/month	2 33.3%	4 57.1%	3 50%	9 47.4%
< 2 events/month	4 66.7%	3 42.9%	3 50%	10 52.6%

Outcome Measures

1. Primary Outcome

Title	Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
Description	The angioedema event rate and the treatment comparisons between each berotralstat dose and placebo in the rate of expert-confirmed angioedema events during the entire dosing period was analyzed using a negative binomial regression model. The number of expert-confirmed angioedema events was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline monthly angioedema event rate) and study (for the combined study analysis) were included as covariates, and the logarithm of duration on treatment was included as an offset variable. The estimated rate of angioedema events for each treatment group, the treatment differences expressed as the angioedema event rate ratio (berotralstat) over placebo rate ratio), and their associated 95% confidence intervals (CIs) were provided from the negative binomial regression model.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data.

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.
Measure Participants	6	7	6
Mean (Standard Deviation) [Angioedema event rate per 28 days]	1.961 (1.3021)	1.089 (0.9168)	2.734 (1.6359)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 110mg Once Daily, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.181
	Comments
	Method	negative binomial regression model
	Comments
Method of Estimation	Estimation Parameter	negative binomial regression model
	Estimated Value	-24.6
	Confidence Interval	(2-Sided) 95%; -50.1 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 150mg Once Daily, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	negative binomial regression model
	Comments
Method of Estimation	Estimation Parameter	negative binomial regression model
	Estimated Value	-49.1
	Confidence Interval	(2-Sided) 95%; -67.5 to -20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.
Description	Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data. Data were analyzed according to randomized treatment.

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.
Measure Participants	6	7	6
Least Squares Mean (Standard Error) [Proportion days with angioedema symptoms]	0.258 (0.0534)	0.118 (0.0500)	0.240 (0.0536)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 110mg Once Daily, Placebo
	Comments	Numerical differences from the placebo treatment in the LSM proportion of the 169 days of treatment with angioedema symptoms.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.814
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	0.018
	Confidence Interval	(2-Sided) 95%; -0.143 to 0.179
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 150mg Once Daily, Placebo
	Comments	Numerical differences from the placebo treatment in the LSM proportion of the 169 days of treatment with angioedema symptoms.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-0.122
	Confidence Interval	(2-Sided) 95%; -0.280 to 0.036
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period
Description	The rate of expert-confirmed angioedema events for the effective treatment period gives an analysis of the efficacy of active treatment after berotralstat had reached steady-state concentrations, given the effective half-life of 150 mg berotralstat in Study BCX7353-106 (Study 106) of 89 hours.
Time Frame	Day 8 through to 24 weeks

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data. Data were analyzed according to randomized treatment.

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.
Measure Participants	6	7	6
Mean (Standard Deviation) [Angioedema event rate per 28 days]	1.988 (1.3422)	1.136 (0.9564)	2.775 (1.6472)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 110mg Once Daily, Placebo
	Comments	In the event that the first secondary endpoint did not meet statistical significance in the hierarchical testing scheme, testing of the second secondary endpoint of rate of expert-confirmed angioedema events during dosing in the effective treatment period for statistical significance would not be completed. Therefore, P-values reported are nominal.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.188
	Comments
	Method	mixed-model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	mixed-model repeated measures analysis
	Estimated Value	24.5
	Confidence Interval	(2-Sided) 95%; -14.7 to 50.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 150mg Once Daily, Placebo
	Comments	In the event that the first secondary endpoint did not meet statistical significance in the hierarchical testing scheme, testing of the second secondary endpoint of rate of expert-confirmed angioedema events during dosing in the effective treatment period for statistical significance would not be completed. Therefore, P-values reported are nominal.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	mixed-model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	mixed-model repeated measures analysis
	Estimated Value	47.6
	Confidence Interval	(2-Sided) 95%; 17.7 to 66.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score)
Description	Change in Quality of Life, on a 1-100 scale, where higher scores indicate more impairment and a decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL is only validated for adults; however, data were collected on all adult and adolescent study subjects.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data. Data were analyzed according to randomized treatment.

Arm/Group Title	Berotralstat 110mg Once Daily	Berotralstat 150mg Once Daily	Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Placebo administered as two 2 matching capsules, orally QD for24 weeks.
Measure Participants	6	7	6
Least Squares Mean (Standard Error) [AE-QoL Total Score Change from baseline]	-9.47 (6.933)	-15.82 (6.424)	3.18 (6.832)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 110mg Once Daily, Placebo
	Comments	Numerical difference in change from baseline of AE-QoL total score between treatment groups. In the event that the first secondary endpoint did not meet statistical significance in the hierarchical testing scheme, testing of the third secondary endpoint of change from baseline in AE-QoL total score at Week 24 for statistical significance would not be completed. P-values that are reported are nominal.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.213
	Comments
	Method	mixed-model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	mixed-model repeated measures analysis
	Estimated Value	-12.65
	Confidence Interval	(2-Sided) 95%; -33.33 to 8.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Berotralstat 150mg Once Daily, Placebo
	Comments	Numerical difference in change from baseline of AE-QoL total score between treatment groups. In the event that the first secondary endpoint did not meet statistical significance in the hierarchical testing scheme, testing of the third secondary endpoint of change from baseline in AE-QoL total score at Week 24 for statistical significance would not be completed. P-values that are reported are nominal.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments
	Method	mixed-model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	mixed-model repeated measures analysis
	Estimated Value	-19.00
	Confidence Interval	(2-Sided) 95%; -39.00 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed until the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE.
Arm/Group Title	Berotralstat 110mg Once Daily		Berotralstat 150mg Once Daily		Placebo
Arm/Group Description	Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.		Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.		Placebo administered as two 2 matching capsules, orally QD for24 weeks.
All Cause Mortality
	Berotralstat 110mg Once Daily		Berotralstat 150mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)		0/6 (0%)
Serious Adverse Events
	Berotralstat 110mg Once Daily		Berotralstat 150mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/7 (0%)		0/6 (0%)
Infections and infestations
pneumonia	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Berotralstat 110mg Once Daily		Berotralstat 150mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		7/7 (100%)		6/6 (100%)
Gastrointestinal disorders
Abdominal discomfort	1/6 (16.7%)	1	0/7 (0%)	0	1/6 (16.7%)	1
Abdominal pain	1/6 (16.7%)	4	1/7 (14.3%)	1	0/6 (0%)	0
Diarrhoea	1/6 (16.7%)	8	1/7 (14.3%)	1	0/6 (0%)	0
Abdominal pain upper	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Dental caries	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Flatulence	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Gastritis	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Nausea	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Oesophageal discomfort	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Toothache	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
General disorders
Pyrexia	1/6 (16.7%)	1	1/7 (14.3%)	1	0/6 (0%)	0
Injection site reaction	1/6 (16.7%)	28	0/7 (0%)	0	0/6 (0%)	0
Infections and infestations
Nasopharyngitis	2/6 (33.3%)	2	2/7 (28.6%)	2	4/6 (66.7%)	5
Otitis media	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Pneumonia	1/6 (16.7%)	2	0/7 (0%)	0	0/6 (0%)	0
Tinea pedis	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Arthropod bite	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Contusion	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Investigations
Platelet count decreased	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Nervous system disorders
Headache	1/6 (16.7%)	1	0/7 (0%)	0	1/6 (16.7%)	1
Somnolence	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Psychiatric disorders
Insomnia	0/6 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Reproductive system and breast disorders
Dysmenorrhoea	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/6 (33.3%)	2	0/7 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	0/6 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1
Dermatitis contact	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Eczema	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Miliaria	1/6 (16.7%)	1	0/7 (0%)	0	0/6 (0%)	0
Pruritus	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Rash	0/6 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0

Limitations/Caveats

These are results from the primary analysis completed at the end of Part 1 only. Results for Part 2 and Part 3 will be available in the final analysis.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.