Trial Outcomes & Findings for Safety and Tolerability of a Novel Malathion Formulation in Children Age 6-24 Months With Head Lice (NCT NCT00752973)

Results Overview

Each patient (aged 6 - 24 months) was assessed at 1 hour (Day 0). The mean percent change (reduction) in plasma and RBC cholinesterase activity from baseline to 1 hr after application was calculated and accompanied by 95% confidence intervals. If the half-widths of the derived confidence intervals are sufficiently narrow, it will demonstrate that any observed reductions in plasma and RBC cholinesterase activity fall within established safety guidelines. Concentration of RBC-cholinesterase (RBC-ChE) and plasma cholinesterase were obtained at baseline, at 1 hr (Day 0) and at 24 hrs (Day 1) after the application of the treatment. Mean percent change (reduction) = (Post treatment value - Baseline)/ Baseline x100.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

12 participants

Primary outcome timeframe

Change from Baseline to 1 hour

Results posted on

2014-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	Malathion Gel 0.5% Treatment Arm Malathion Gel 0.5% treatment MALG (Malathion Gel 0.5%) Treatment: MALG applied for 30 minutes
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Tolerability of a Novel Malathion Formulation in Children Age 6-24 Months With Head Lice

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MALG Treatment Arm n=12 Participants MALG treatment MALG (malathion) Treatment: MALG applied for 30 minutes
Age, Continuous	17.5 months STANDARD_DEVIATION 4.64 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change from Baseline to 1 hour

Population: 10 subjects with obtained blood sample. subject 01-003: Study coordinator was unable to obtain blood sample post treatment at Visit 1, Day 0. subject 01-004: At Visit 1 Day 0 (post treatment), Blood sample could not be obtained even after two attempts.

Each patient (aged 6 - 24 months) was assessed at 1 hour (Day 0). The mean percent change (reduction) in plasma and RBC cholinesterase activity from baseline to 1 hr after application was calculated and accompanied by 95% confidence intervals. If the half-widths of the derived confidence intervals are sufficiently narrow, it will demonstrate that any observed reductions in plasma and RBC cholinesterase activity fall within established safety guidelines. Concentration of RBC-cholinesterase (RBC-ChE) and plasma cholinesterase were obtained at baseline, at 1 hr (Day 0) and at 24 hrs (Day 1) after the application of the treatment. Mean percent change (reduction) = (Post treatment value - Baseline)/ Baseline x100.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=10 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants With a Change in Cholinesterase Level at 1 Hour (Day 0). Plasma	-1.8 percentage change in cholinesterase Interval -3.9 to 0.4
Participants With a Change in Cholinesterase Level at 1 Hour (Day 0). RBC cholinesterase	-0.5 percentage change in cholinesterase Interval -3.5 to 2.6

PRIMARY outcome

Timeframe: Change from baseline to 24 hrs (1 day)

Population: 11 subjects with obtained blood sample. subject 01-004: At Visit 2, Day 1 Lab could not perform testing due to sample not suitable for testing. Because only 2ml blood was able to collected after multiple attempts.

Each patient was assessed at Day 1 and the mean percent reduction in plasma and RBC cholinesterase activity from baseline to 24 hr after application was calculated and accompanied by 95% confidence intervals. Concentration of RBC-cholinesterase (RBC-ChE) and plasma cholinesterase were obtained at baseline, at 1 hr (Day 0) and at 24 hrs (Day 1) after the application of the treatment. Mean percent reduction = (Post treatment value - Baseline)/ Baseline x100.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=11 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants With a Change in Cholinesterase Level at 24 Hrs (1 Day). Plasma Cholinesterase	-1.7 percentage change in cholinesterase Interval -5.0 to 1.7
Participants With a Change in Cholinesterase Level at 24 Hrs (1 Day). RBC Cholinesterase	1.4 percentage change in cholinesterase Interval -1.8 to 4.6

PRIMARY outcome

Timeframe: at Baseline

Participants with any of the following symptoms of cholinesterase inhibition as numbered below were considered to have Clinical evidence of cholinesterase inhibition. 1. Abnormal heart rate. 2. Diarrhea or abdominal cramps. 3. Inappropriate sweating. 4. Pupillary miosis (constriction). 5. Respiratory difficulty such as chest tightness or wheezing. One participant had wheezing as medical history which continued without increase in severity throughout the treatment.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=12 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants With the Clinical Evidence of Cholinesterase Inhibition	8.3 percentage of participants

PRIMARY outcome

Timeframe: at 1 hr (Day 0)

Participants with any of the following symptoms of cholinesterase inhibition as numbered below were considered to have Clinical evidence cholinesterase inhibition : 1. Abnormal heart rate. 2. Diarrhea or abdominal cramps. 3. Inappropriate sweating. 4. Pupillary miosis (constriction). 5. Respiratory difficulty such as chest tightness or wheezing. One participants had wheezing as medical history which continued without increase in severity throughout the treatment.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=12 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants With the Clinical Evidence of Cholinesterase Inhibition	8.3 percentage of participants

PRIMARY outcome

Timeframe: at 24 hrs (Day 1)

Participants with any of the following symptoms of cholinesterase inhibition as numbered below were considered to have Clinical evidence of cholinesterase inhibition : 1. Abnormal heart rate. 2. Diarrhea or abdominal cramps. 3. Inappropriate sweating. 4. Pupillary miosis (constriction). 5. Respiratory difficulty such as chest tightness or wheezing. One participants had wheezing as medical history which continued without increase in severity throughout the treatment.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=12 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants With the Clinical Evidence of Cholinesterase Inhibition	0 percentage of participants

PRIMARY outcome

Timeframe: Day 7±1 and Day 14 or Day 21

Population: No statistical analysis provided for Clinical Cure

No live lice (including adults and nymphs) and nits at Day 7±1 and final lice assessment on either Day 14 (subjects not requiring retreatment) or Day 21 (for retreated subjects).

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=12 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Participants Clinically Cured of Head Lice 14 Days After Last Treatment	12 participants cured of lice

SECONDARY outcome

Timeframe: Participants were followed for a minimum of 14 days (1 treatment) and a maximum of 21 days (2 treatments)

Population: A total of 12 subjects were enrolled. All of them used the study drug for at least one dose of the treatment. At Day 0 the study drug was to be used. At Day 7 if subject presented with live lice they were provided a second treatment. The subjects may used it for 1 (for subjects not requiring retreatment) or 2 (for retreated subjects).

To evaluate the safety of Malathion Gel, 0.5% based upon reported adverse events and observed scalp reactions. Additional safety assessments included eye Irritation.

Outcome measures

Outcome measures
Measure	MALG (Malathion Gel, 0.5% )Treatment Arm n=12 Participants MALG (Malathion Gel, 0.5% ) treatment MALG (Malathion Gel, 0.5% ) Treatment: MALG applied for 30 minutes Two subjects had out of range RBC cholinesterase values. One subject had out of range (low) value at baseline and One subject had out of range (low) value 1 h post treatment. Both these values were considered to be not clinically significant by the investigator.
Evaluation of the Local Safety of Malathion Gel, 0.5% Based Upon Reported Adverse Events and Observed Scalp Reactions. No sign of irritation	11 participants
Evaluation of the Local Safety of Malathion Gel, 0.5% Based Upon Reported Adverse Events and Observed Scalp Reactions. Slight noticeable erythema + slight infiltration	1 participants
Evaluation of the Local Safety of Malathion Gel, 0.5% Based Upon Reported Adverse Events and Observed Scalp Reactions. No conjunctival irritation	12 participants

Adverse Events

MALG Treatment Arm

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	MALG Treatment Arm n=12 participants at risk MALG treatment MALG (malathion) Treatment: MALG applied for 30 minutes
Respiratory, thoracic and mediastinal disorders Cough	25.0% 3/12 • Number of events 3 • 22 months
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Number of events 1 • 22 months
Injury, poisoning and procedural complications Head injury	8.3% 1/12 • Number of events 1 • 22 months
Respiratory, thoracic and mediastinal disorders Wheezing	8.3% 1/12 • Number of events 1 • 22 months

Additional Information

Director, Clinical Research

Taro Pharmaceuticals U.S.A., Inc.

Phone: 914 345 9001

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place