Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers

• Sponsor: Medicines Development for Global Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT03012828
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 6
• Duration (Months): 3.9
• Patients Per Site Per Month: 15.2

Study Details

Study Description

Brief Summary

This study will investigate the effect of a single oral dose of moxidectin on the QT interval associated with moxidectin plasma concentrations.

The effect of moxidectin on other ECG intervals, and on safety, will also be assessed, as will preliminary pharmacokinetics and metabolism

Condition or Disease	Intervention/Treatment	Phase
QT Effects in Healthy Volunteers	Drug: Moxidectin; Other: Placebo	Phase 1

Detailed Description

Moxidectin is being developed as a treatment for Onchocerciasis (river blindness), a serious, debilitating, disease caused by a parasitic worm, Onchocerca volvulus.

Five dose levels of moxidectin will be administered to healthy volunteers and ECG assessments undertaken at pre-specified pharmacokinetic time points to correlate QT interval with moxidectin concentration in plasma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Potential Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers
• Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Moxidectin 4mg 10 subjects will receive a single oral dose of moxidectin 4mg	Drug: Moxidectin; Moxidectin is a broad spectrum macrocyclic lactone endectocide
Experimental: Moxidectin 8mg 10 subjects will receive a single oral dose of moxidectin 8mg	Drug: Moxidectin; Moxidectin is a broad spectrum macrocyclic lactone endectocide
Experimental: Moxidectin 16mg 10 subjects will receive a single oral dose of moxidectin 16mg	Drug: Moxidectin; Moxidectin is a broad spectrum macrocyclic lactone endectocide
Experimental: Moxidectin 24mg 10 subjects will receive a single oral dose of moxidectin 24mg	Drug: Moxidectin; Moxidectin is a broad spectrum macrocyclic lactone endectocide
Experimental: Moxidectin 36mg 10 subjects will receive a single oral dose of moxidectin 36mg	Drug: Moxidectin; Moxidectin is a broad spectrum macrocyclic lactone endectocide
Placebo Comparator: Placebo 10 subjects will receive a single oral dose of placebo	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose [Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing]

   Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.

Secondary Outcome Measures

1. Concentrations of Moxidectin in Plasma [Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing]

   Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.

Other Outcome Measures

1. Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs) [At Baseline and Days 1, 2, 3, 4, 22 and Week 12]

   Changes from baseline in QTcF exceeding regulatory standard categorical limits (> 30msec change or exceeding 450msec). Report applies to changes of 30msec - </= 60msec only

2. Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS) [Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing]

   Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy male between 18 and 50 years of age (inclusive);

2. Body mass index (BMI) of 18 to 30 kg/m2 (inclusive) and a minimum weight of 50 kg (110 lbs);

3. Biologically or surgically sterile or must commit to using a reliable method of birth control, in the opinion of the investigator, from Screening through the duration of the study;

4. Willing and able to give written informed consent.

Exclusion Criteria:

1. Unwilling to abstain from alcohol, caffeine, xanthine containing products, Seville oranges, grapefruit juices, and fish liver oils within 72 hours before Check in (Day -1) and throughout the inpatient period of the study;

2. Less than 1 bowel movement every 24 hours in the absence of any laxative, suppository, or enema use during the month before Screening;

3. Abnormal fecal consistency within 24 hours of Check in (Day -1);

4. Clinically relevant abnormal findings on medical history, clinical laboratory test results, vital sign measurements, safety 12 lead ECG results, or physical examination at Screening or Baseline which, in the opinion of the investigator, would interfere with dosing, jeopardize the safety of the subject, or impact the validity of the study results;

5. History of clinically significant dermatologic, gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the investigator, would interfere with dosing, jeopardizes the safety of the subject, or impacts the validity of the study results;

6. History or hypersensitivity or allergic reactions to ivermectin, moxidectin, or any of the ingredients in the study drug as described in the Investigator's Brochure;

7. Any condition that may affect oral drug absorption (eg, previous surgery on the gastrointestinal tract including removal of parts of the stomach, bowel, liver, gall bladder, or pancreas);

8. History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects are also excluded if there is a family history of long QT syndrome or Brugada syndrome;

9. A sustained supine systolic blood pressure >150 mm Hg or <90 mm Hg or a supine diastolic blood pressure >95 mm Hg or <50 mm Hg at Screening or Check in (Day -1). Blood pressure may be retested twice in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic blood pressure values are outside of the stated limits after 3 assessments, and the subject will not to be randomized;

10. A resting heart rate (HR) of <40 beats per minute (bpm) or >100 bpm when vital signs are measured at Screening or Check in (Day -1);

11. An uninterpretable or abnormal screening ECG indicating a second or third degree atrioventricular block, or 1 or more of the following: QRS interval >110 milliseconds (msec); QT interval corrected by Fridericia's formula (QTcF) >450 msec; PR interval

200 msec; or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant;

1. Concomitant use of prescription medications, including medications known to prolong the corrected QT interval (QTc) or herbal preparations, within 14 days or 5 half-lives (whichever is longer) before study drug dosing, or use of an over the counter (OTC) medication or vitamins within 7 days before study drug dosing;

2. Received an investigational drug during the 30 days, or 5 half lives of the study drug (whichever is longer), before Check in (Day -1) or is planning to receive another investigational drug at any time during the study;

3. History or presence of alcohol abuse (defined as consumption of more than 210 mL of alcohol per week, or the equivalent of fourteen 4 ounce [oz] glasses of wine or fourteen 12 oz cans/bottles of beer or wine coolers per week) within 6 months before Screening or positive alcohol test at Screening or Check-in (Day -1);

4. History or presence of substance abuse within the past 2 years or positive drug screen test at Screening or Check in (Day -1);

5. Current use or has used tobacco- or nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 14 days before study drug dosing;

6. Blood donation or significant blood loss within 30 days before Check-in (Day -1) or donated plasma within 7 days before Check-in (Day -1);

7. Presence of hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or hepatitis C virus at Screening;

8. Poor venous access in both arms;

9. Unable to understand verbal or written English or any other language for which a certified translation of the informed consent form is available;

10. For any reason, is deemed by the investigator or medically qualified designee to be inappropriate for this study, including a subject who is unable to communicate or cooperate with the investigator, and/or is unwilling to comply with protocol defined procedures and complete the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spaulding Clinical	West Bend	Wisconsin	United States	53095

Sponsors and Collaborators

• Medicines Development for Global Health

Investigators

• Study Director: Mark Sullivan, Sponsor GmbH

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2017
• Statistical Analysis Plan - Mar 1, 2017

More Information

Publications

None provided.

• Responsible Party: Medicines Development for Global Health
• ClinicalTrials.gov Identifier: NCT03012828
• Other Study ID Numbers: MDGH-MOX-1008
• First Posted: Jan 6, 2017
• Last Update Posted: Mar 14, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Moxidectin

Study Results

Participant Flow

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg	Placebo
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin	10 subjects will receive a single oral dose of placebo Placebo
Period Title: Overall Study
STARTED	10	10	10	10	10	10
COMPLETED	9	10	8	10	8	8
NOT COMPLETED	1	0	2	0	2	2

Baseline Characteristics

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg	Placebo	Total
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin	10 subjects will receive a single oral dose of placebo Placebo	Total of all reporting groups
Overall Participants	10	10	10	10	10	10	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.1 (7.77)	30.4 (8.73)	30.9 (8.32)	31.2 (8.27)	30.2 (8.87)	32.3 (6.72)	32.0 (8.15)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	10 100%	10 100%	10 100%	10 100%	10 100%	10 100%	60 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%	2 20%	1 10%	1 10%	0 0%	0 0%	6 10%
Not Hispanic or Latino	8 80%	8 80%	9 90%	9 90%	10 100%	10 100%	54 90%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 10%	0 0%	1 10%	0 0%	2 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	1 10%	0 0%	1 1.7%
Black or African American	3 30%	7 70%	4 40%	5 50%	5 50%	5 50%	29 48.3%
White	7 70%	3 30%	5 50%	4 40%	3 30%	5 50%	27 45%
More than one race	0 0%	0 0%	0 0%	1 10%	0 0%	0 0%	1 1.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	10 100%	10 100%	10 100%	10 100%	60 100%
Body Mass Index (BMI) (kilogram /meter squared (kg/m2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram /meter squared (kg/m2)]	26.2 (3.74)	24.9 (3.35)	25.8 (3.71)	25.1 (3.00)	26.7 (3.09)	26.1 (3.11)	25.8 (3.26)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose
Description	Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.
Time Frame	Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing

Outcome Measure Data

Analysis Population Description

The ECG population included all subjects who received one dose of study drug and have at least 1 pair of pre-dose and post-dose QTc interval and was used in the model.

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg	Placebo	All Subjects
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin	10 subjects will receive a single oral dose of placebo Placebo	50 subjects received a single dose of between 4mg and 36mg of moxidectin. 10 subjects received a dose of placebo,
Measure Participants	10	10	10	10	10	10	60
Mean (90% Confidence Interval) [millseconds]	-5.1	-4.5	-4.5	-6.3	-3.9	-2.9	-0.0077

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Subjects
	Comments	The primary analysis used a mixed-effects model to explore the relationship between the time-matched, baseline-adjusted QTcF (delta (d)QTcF) and moxidectin concentrations. dQTcF was a dependent variable and treatment, time point, and treatment by time point interaction as the independent variables with baseline QTcF as a covariate and time-matched concentrations of moxidectin as a covariate with random effects of intercept and slope for each subject.Concentrations of zero were used for placebo.
	Type of Statistical Test	Other
	Comments	The model was used for predicting population average and 90% 2-sided bootstrapped CI of the baseline-adjusted difference between active and placebo at each time point bound at clinically relevant concentrations.
Statistical Test of Hypothesis	p-Value	0.4727
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.0077
	Confidence Interval	(2-Sided) 90%; -0.0255 to 0.0101
	Parameter Dispersion	Type: Value:
	Estimation Comments	The primary mixed effects model analysis revealed a nearly flat dQTcF - plasma concentration gradient

2. Secondary Outcome

Title	Concentrations of Moxidectin in Plasma
Description	Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.
Time Frame	Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population - includes all subjects who received at least 1 dose of moxidectin and provide an adequate number of plasma samples for determination of PK parameters, analyzed according to drug received.

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin
Measure Participants	10	10	10	10	10
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter]	27.2 (30.6)	56.7 (20.8)	133 (27.1)	176 (18.7)	247 (19.7)

3. Other Pre-specified Outcome

Title	Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)
Description	Changes from baseline in QTcF exceeding regulatory standard categorical limits (> 30msec change or exceeding 450msec). Report applies to changes of 30msec - </= 60msec only
Time Frame	At Baseline and Days 1, 2, 3, 4, 22 and Week 12

Outcome Measure Data

Analysis Population Description

Safety population - all who received at least one dose of study drug

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg	Placebo
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin	10 subjects will receive a single oral dose of placebo Placebo
Measure Participants	10	10	10	10	10	10
Number [participants]	1 10%	0 0%	0 0%	0 0%	1 10%	1 10%

4. Other Pre-specified Outcome

Title	Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)
Description	Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.
Time Frame	Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing

Outcome Measure Data

Analysis Population Description

ECG population - all subjects who receive one dose of study drug and have at least one pair of pre-dose and post-dose QTc data, analyzed as randomized

Arm/Group Title	Moxidectin 4mg	Moxidectin 8mg	Moxidectin 16mg	Moxidectin 24mg	Moxidectin 36mg	Placebo	All Subjects
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin	10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin	10 subjects will receive a single oral dose of placebo Placebo	50 subjects received a single dose of moxidectin between 4mg and 36mg and 10 subjects received placebo
Measure Participants	10	10	10	10	10	10	60
Change in Heart rate (HR)	-1.0	0.5	-1.1	-3.6	-1.5	-2.9	-0.005
Change in PR interval	2.2	-0.1	-2.1	4.6	-3.5	-1.8	-0.002
Change in QRS interval	-1.6	-0.7	0.4	-0.8	0.4	1.2	0.004

Adverse Events

Time Frame	Adverse events were collected over the full 12 weeks of study follow-up
Arm/Group Title	Moxidectin 4mg		Moxidectin 8mg		Moxidectin 16mg		Moxidectin 24mg		Moxidectin 36mg		Placebo
Arm/Group Description	10 subjects will receive a single oral dose of moxidectin 4mg Moxidectin		10 subjects will receive a single oral dose of moxidectin 8mg Moxidectin		10 subjects will receive a single oral dose of moxidectin 16mg Moxidectin		10 subjects will receive a single oral dose of moxidectin 24mg Moxidectin		10 subjects will receive a single oral dose of moxidectin 36mg Moxidectin		10 subjects will receive a single oral dose of placebo Placebo
All Cause Mortality
	Moxidectin 4mg		Moxidectin 8mg		Moxidectin 16mg		Moxidectin 24mg		Moxidectin 36mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Moxidectin 4mg		Moxidectin 8mg		Moxidectin 16mg		Moxidectin 24mg		Moxidectin 36mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Moxidectin 4mg		Moxidectin 8mg		Moxidectin 16mg		Moxidectin 24mg		Moxidectin 36mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		3/10 (30%)		1/10 (10%)		0/10 (0%)		3/10 (30%)		1/10 (10%)
Eye disorders
Eye irritation	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Abdominal discomfort	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
General disorders
Medical device site reaction	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Investigations
AST increased	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Blood bilirubin increased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Blood cholesterol increased	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Neck pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Pain in extremity	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Dizziness	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Headache	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Oropharyngeal pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (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.