Safety, PK and Effectiveness of IV Peramivir in Elderly and Higher Risk Subjects With Uncomplicated Influenza

• Sponsor: BioCryst Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02635724
• Collaborator: (none)
• Enrollment: 74
• Locations: 15
• Arm: 1
• Duration (Months): 33
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the safety, pharmacokinetics and effectiveness of a single dose of 600 mg IV peramivir in the treatment of elderly subjects with acute uncomplicated influenza infection and in subjects with acute uncomplicated influenza infection at higher risk for influenza complications. All subjects will receive IV peramivir.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Peramivir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Single-arm, Open-label, Study to Evaluate the Safety, Pharmacokinetics and Effectiveness of Intravenous Peramivir in Elderly Subjects With Acute Uncomplicated Influenza Infection and in Subjects With Acute Uncomplicated Influenza Infection at Higher Risk for Influenza Complications
• Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peramivir Single dose 600 mg IV injection	Drug: Peramivir; Other Names: Rapivab

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability, as Measured by the Number of Adverse Events. [14 days]

   Safety was evaluated through assessment of Adverse Events (AEs).

Secondary Outcome Measures

1. Plasma Exposure of IV Peramivir as Measured by Drug Concentrations up to 3 Hours Post Infusion [up to 3 hours post peramivir infusion]

   Up to 3 plasma samples will be drawn, where possible: immediately following infusion, 30 mins to 1 hr post-infusion & 1 to 3 hrs post-infusion. Maximum concentration (Cmax), area under the concentration vs. time curve (AUC) from time 0 to 1 hour (AUC0-1), AUC from time 0 to 1.5 hours (AUC0-1.5), and AUC from time 0 to the last measurable time point (AUC0-last) were calculated in Phoenix® WinNonlin® v6.4. No summary statistics were reported due to the variation in the infusion time and sampling times.

2. Time to Resolution of Fever [14 days]

   Time for fever resolution based on subject diary record of temperature recorded twice daily. A subject had resolution of fever if he/she had an oral temperature < 37.4°C/99.4°F oral and no antipyretic medications were taken for at least 12 hours. The time to resolution of fever was estimated for each age group and overall using the Kaplan-Meier method with temperature and symptom relief medication information obtained from the Subject Diary data. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment.

3. Time to Resolution of Influenza Symptoms [14 days]

   Subjects were asked to provide an assessment of 7 influenza symptoms (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) on a 4-point severity scale (0, absent; 1, mild; 2, moderate; 3, severe) beginning at Screening then twice daily beginning on Day 1 through to Day 13, and prior to the subject's clinic visit on Day 14. Once all symptoms were scored a 0 or 1 for at least 48 hours, recordings were discontinued. The time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 21.5-hour period (24 hours less 10%), where all symptoms of influenza were recorded as none (0) or mild (1), was estimated overall and for each age group using the Kaplan-Meier method.

4. Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. [Change from baseline assessed on days 3, 7 and 14.]

   Change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group.

5. Time to Reduction in Viral Shedding [14 days]

   Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14.

6. Incidence of Influenza-related Complications [14 days]

   Study personnel evaluated the subject at Screening and Days 3, 7, and 14 for the presence of clinical signs and/or symptoms of the following influenza-related complications: Sinusitis, Otitis media, Bronchitis & Pneumonia. Note that subjects with clinical signs and/or symptoms consistent with bacterial infections, including otitis media, bronchitis, sinusitis, and/or pneumonia at Screening, were not eligible for enrollment in this study. If an influenza-related complication was suspected, then a targeted physical examination was to be conducted to confirm the presence or absence of the influenza-related complication.

7. Time to Return to Usual Activities [14 days]

   The ability to perform usual daily activities was assessed on a VAS (Visual Analogue Scale), where 0 indicates "unable to perform usual activities at all" and 10 indicates "able to perform usual activities.". The time to return to usual activities was the number of days from initiation of study drug until the subject recorded a rating of 10 (able to perform all usual activities fully) on the VAS; this was estimated for each age group and overall using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A positive influenza Rapid Antigen Test (RAT) and/or a FDA-approved PCR test and at least one clinical sign or symptom consistent with acute influenza infection as listed below OR

• Clinical signs and symptoms consistent with acute influenza infection consisting of an oral temperature ≥ 100°F (37.8°C) with at least one respiratory symptom of at least moderate severity (cough or rhinitis) and at least one constitutional symptom of at least moderate severity (myalgia [aches and pains], headache, feverishness, or fatigue)

• Influenza symptom onset < 48 hours. However, due to historically delayed presentation for medical care in the adult population, approximately 20% of the elderly population may be enrolled with symptoms starting > 48-hours but ≤ 72-hours

Exclusion Criteria:

• Women who plan to breast-feed for the first 48 hours after study drug administration

• Subjects requiring hospital admission to treat medical condition(s) which could represent complications of influenza.

• Recent worsening of any chronic medical condition consistent with complications of influenza

• Current evidence of a bacterial infection requiring antibiotic treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peramivir Investigational Site	Brooksville	Florida	United States
2	Peramivir Investigational Site	Lakeland	Florida	United States
3	Peramivir Investigational Site	Miami	Florida	United States
4	Peramivir Investigational Site	Saint Petersburg	Florida	United States
5	Peramivir Investigational Site	Tampa	Florida	United States
6	Peramivir investigative site	Indianapolis	Indiana	United States
7	Peramivir investigative site	Detroit	Michigan	United States
8	Peramivir Investigational Site	Dayton	Ohio	United States
9	Peramivir investigative site	Smithfield	Pennsylvania	United States
10	Peramivir Investigational Site	Houston	Texas	United States
11	Peramivir Investigative Site	San Antonio	Texas	United States
12	Peramivir investigative site	Splendora	Texas	United States
13	Peramivir Investigational Site	Draper	Utah	United States
14	Peramivir Investigational Site	Salt Lake City	Utah	United States
15	Peramivir investigative site	South Jordan	Utah	United States

Sponsors and Collaborators

• BioCryst Pharmaceuticals

Investigators

• Principal Investigator: Carol Clark, MD, Prof., Dept. of Emergency Medicine, Oakland University, William Beaumont School of Medicine, Royal Oak, MI

Study Documents (Full-Text)

• Study Protocol - Aug 9, 2017
• Statistical Analysis Plan - Jun 13, 2018

More Information

Publications

None provided.

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02635724
• Other Study ID Numbers: BCX1812-306
• First Posted: Dec 21, 2015
• Last Update Posted: Mar 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by BioCryst Pharmaceuticals: Acute uncomplicated; Elderly
• Additional relevant MeSH terms: Influenza, Human; Peramivir

Study Results

Participant Flow

Pre-assignment Detail	A single dose of IV peramivir was administered to elderly subjects (≥ 65 years old) and at risk subjects with acute uncomplicated influenza. Subjects received a single IV dose of 600 mg peramivir if they had creatinine clearance (CLCR) ≥ 50 mL/min and a reduced dose if they had CLCR < 50 mL/min (200 mg for CLCR 30 to 49 mL/min and 100 mg for CLCR 10 to 29 mL/min).

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk, including pregnant women, residents of long-term care facilities, American Indians and Alaskan Natives, as well as those with comorbidities (e.g. asthma, heart disease, diabetes) that increased the risk of complications.	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Period Title: Overall Study
STARTED	41	26	7
ITT Population	41	26	7
Safety Population	41	25	7
ITTI Population	28	19	5
E-R Population	28	19	5
COMPLETED	41	25	7
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)	Total
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years	Total of all reporting groups
Overall Participants	41	25	7	73
Age (Age at screening (years)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Age at screening (years)]	43.1 (10.67)	68.4 (3.10)	81.1 (3.03)	55.4 (16.62)
Sex: Female, Male (Count of Participants)
Female	29 70.7%	20 80%	4 57.1%	53 72.6%
Male	12 29.3%	5 20%	3 42.9%	20 27.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.4%	0 0%	0 0%	1 1.4%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 4.9%	2 8%	0 0%	4 5.5%
White	37 90.2%	23 92%	7 100%	67 91.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.4%	0 0%	0 0%	1 1.4%
Baseline Influenza Viral Titre (participants) [Number]
Positive	27 65.9%	15 60%	2 28.6%	44 60.3%
Negative	12 29.3%	3 12%	3 42.9%	18 24.7%
Missing	2 4.9%	7 28%	2 28.6%	11 15.1%
Baseline Temperature Status (participants) [Number]
Normal	16 39%	9 36%	5 71.4%	30 41.1%
Fever	25 61%	16 64%	2 28.6%	43 58.9%
Baseline Composite Influenza Symptom Score (Composite Influenza Symptom Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Composite Influenza Symptom Score]	14 (3.4)	15 (3.0)	10 (5.1)	14 (3.6)

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability, as Measured by the Number of Adverse Events.
Description	Safety was evaluated through assessment of Adverse Events (AEs).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	41	25	7
Subjects with at Least 1 Adverse Event	17 41.5%	9 36%	1 14.3%
Subjects with at Least 1 Adverse Event Related to Study Drug	5 12.2%	3 12%	0 0%
Subjects with at Least 1 Adverse Event Leading to Study Discontinuation	0 0%	0 0%	0 0%
Subjects with at Least 1 Severe or Life-Threatening Adverse Event	0 0%	1 4%	0 0%
Subjects with at Least 1 Severe or Life-Threatening Adverse Event Related to Study Drug	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Plasma Exposure of IV Peramivir as Measured by Drug Concentrations up to 3 Hours Post Infusion
Description	Up to 3 plasma samples will be drawn, where possible: immediately following infusion, 30 mins to 1 hr post-infusion & 1 to 3 hrs post-infusion. Maximum concentration (Cmax), area under the concentration vs. time curve (AUC) from time 0 to 1 hour (AUC0-1), AUC from time 0 to 1.5 hours (AUC0-1.5), and AUC from time 0 to the last measurable time point (AUC0-last) were calculated in Phoenix® WinNonlin® v6.4. No summary statistics were reported due to the variation in the infusion time and sampling times.
Time Frame	up to 3 hours post peramivir infusion

Outcome Measure Data

Analysis Population Description

73 subjects from the ITT population had sufficient PK samples collected for inclusion in the peramivir PK analysis

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	41	25	7
AUC0-last	42400 (15630)	68300 (116800)	64600 (66380)
AUC0-1	30600 (15260)	53600 (107400)	54400 (63620)
AUC0-1.5	38200 (12800)	85800 (168000)	35000 (0)

3. Secondary Outcome

Title	Time to Resolution of Fever
Description	Time for fever resolution based on subject diary record of temperature recorded twice daily. A subject had resolution of fever if he/she had an oral temperature < 37.4°C/99.4°F oral and no antipyretic medications were taken for at least 12 hours. The time to resolution of fever was estimated for each age group and overall using the Kaplan-Meier method with temperature and symptom relief medication information obtained from the Subject Diary data. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intent to treat infected (ITTI) population. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment; this included 1 subject in the 'At Risk (<65 years)' group. Twelve subjects were excluded from summaries due to missing data or events resolving prior to initiation of study drug.

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	22	14	4
Median (95% Confidence Interval) [hours]	41.5	29.3	9.4

4. Secondary Outcome

Title	Time to Resolution of Influenza Symptoms
Description	Subjects were asked to provide an assessment of 7 influenza symptoms (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) on a 4-point severity scale (0, absent; 1, mild; 2, moderate; 3, severe) beginning at Screening then twice daily beginning on Day 1 through to Day 13, and prior to the subject's clinic visit on Day 14. Once all symptoms were scored a 0 or 1 for at least 48 hours, recordings were discontinued. The time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 21.5-hour period (24 hours less 10%), where all symptoms of influenza were recorded as none (0) or mild (1), was estimated overall and for each age group using the Kaplan-Meier method.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intent to treat infected (ITTI) population. Subjects who did not experience alleviation of symptoms were censored at the date of their last non-missing post-baseline assessment; this included 5 subjects in the 'At Risk (<65 years)' group, 4 subjects in the 'Elderly (65-75 years)' group and 2 subjects in the 'Very Elderly (>75 years)' group.

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	28	19	5
Mean (Standard Deviation) [hours]	124.8 (10.59)	114.5 (20.37)	54.0 (9.45)

5. Secondary Outcome

Title	Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment.
Description	Change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group.
Time Frame	Change from baseline assessed on days 3, 7 and 14.

Outcome Measure Data

Analysis Population Description

The Intent To Treat Infected (ITTI) population included all subjects who were enrolled, received study drug, and had confirmed influenza A and/or B by PCR. Eight subjects were excluded due to a negative or missing BL titer.

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	27	15	2
Baseline	4.50	4.45	4.70
Day 3 - Change from baseline	-3.25	-3.00
Day 7 - Change from baseline	-4.00	-2.13
Day 14 - Change from baseline	-3.88	-3.25

6. Secondary Outcome

Title	Time to Reduction in Viral Shedding
Description	Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intent to treat infected (ITTI) population + ITT population with positive baseline influenza viral titers [> 0.5 log10 TCID50/mL]. Eight subjects were excluded due to a negative or missing Baseline titer.

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	27	15	2
Baseline	27 65.9%	15 60%	2 28.6%
Day 3	13 31.7%	4 16%	0 0%
Day 7	0 0%	0 0%	0 0%
Day 14	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Incidence of Influenza-related Complications
Description	Study personnel evaluated the subject at Screening and Days 3, 7, and 14 for the presence of clinical signs and/or symptoms of the following influenza-related complications: Sinusitis, Otitis media, Bronchitis & Pneumonia. Note that subjects with clinical signs and/or symptoms consistent with bacterial infections, including otitis media, bronchitis, sinusitis, and/or pneumonia at Screening, were not eligible for enrollment in this study. If an influenza-related complication was suspected, then a targeted physical examination was to be conducted to confirm the presence or absence of the influenza-related complication.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intent-to-treat infected (ITTI) population

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	28	19	5
Otitis	1 2.4%	0 0%	0 0%
Sinusitis	0 0%	1 4%	0 0%
Bronchitis	2 4.9%	2 8%	0 0%
Pneumonia	0 0%	1 4%	0 0%

8. Secondary Outcome

Title	Time to Return to Usual Activities
Description	The ability to perform usual daily activities was assessed on a VAS (Visual Analogue Scale), where 0 indicates "unable to perform usual activities at all" and 10 indicates "able to perform usual activities.". The time to return to usual activities was the number of days from initiation of study drug until the subject recorded a rating of 10 (able to perform all usual activities fully) on the VAS; this was estimated for each age group and overall using the Kaplan-Meier method.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Subjects who did not return to normal activities were censored at the time of their last non-missing post-baseline assessment; this included 9 subjects in the 'At Risk (<65 years)' group, 12 subjects in the 'Elderly (65-75 years)' group and 2 subjects in the 'Very Elderly (>75 years)' group. Two subjects were excluded from summaries due to missing data or events resolving prior to initiation of study treatment.

Arm/Group Title	At Risk (<65 Years)	Elderly (65-75 Years)	Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk	A single IV dose of peramivir was administered to adults aged 65 to 75 years	A single IV dose of peramivir was administered to adults aged over 75 years
Measure Participants	27	19	4
Mean (Standard Deviation) [days]	10.0 (0.59)	12.1 (0.91)	9.8 (2.76)

Adverse Events

Time Frame	Reports of AEs were to be collected from the time the subject signed the informed consent through to the follow-up period ending on Day 14.
Adverse Event Reporting Description	Adverse events were graded through use of the Division of Acquired Immune Deficiency Syndrome (DAIDS) Tables for Grading Adult and Pediatric Adverse Experiences. Influenza-related complications were not considered AEs unless they met the criteria for an SAE.
Arm/Group Title	At Risk (<65 Years)		Elderly (65-75 Years)		Very Elderly (>75 Years)
Arm/Group Description	A single IV dose of peramivir was administered to adults considered at risk		A single IV dose of peramivir was administered to adults aged 65 to 75 years		A single IV dose of peramivir was administered to adults aged over 75 years
All Cause Mortality
	At Risk (<65 Years)		Elderly (65-75 Years)		Very Elderly (>75 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/25 (0%)		0/7 (0%)
Serious Adverse Events
	At Risk (<65 Years)		Elderly (65-75 Years)		Very Elderly (>75 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/25 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	At Risk (<65 Years)		Elderly (65-75 Years)		Very Elderly (>75 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/41 (41.5%)		9/25 (36%)		1/7 (14.3%)
Ear and labyrinth disorders
Cerumen impaction	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Eustachian tube dysfunction	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Eye disorders
Eye pain	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Vision blurred	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Gastrointestinal disorders
Diarrhoea	3/41 (7.3%)	3	1/25 (4%)	1	1/7 (14.3%)	1
Abdominal pain upper	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
General disorders
Infusion site extravasation	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Infections and infestations
Cystitis	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Urinary tract infection	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Hordeolum	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Pharyngitis	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Respiratory tract infection	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Vulvovaginal mycotic infection	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Investigations
Breath sounds abnormal	2/41 (4.9%)	2	0/25 (0%)	0	0/7 (0%)	0
Blood pressure increased	1/41 (2.4%)	1	1/25 (4%)	1	0/7 (0%)	0
Blood lactate dehydrogenase increased	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Blood pressure diastolic increased	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Blood urine present	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Carbon dioxide decreased	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Nitrite urine present	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Red blood cells urine positive	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
White blood cells urine positive	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Nervous system disorders
Dizziness	1/41 (2.4%)	1	2/25 (8%)	2	0/7 (0%)	0
Migraine	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Psychiatric disorders
Insomnia	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Wheezing	2/41 (4.9%)	2	1/25 (4%)	1	1/7 (14.3%)	1
Bronchospasm	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0
Dyspnoea	1/41 (2.4%)	1	0/25 (0%)	0	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/41 (0%)	0	2/25 (8%)	2	0/7 (0%)	0
Dermatitis	0/41 (0%)	0	1/25 (4%)	1	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

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.