Trial Outcomes & Findings for Oral Ketamine for Control of Chronic Pain in Children (NCT NCT01369680)

Last Updated: 2013-02-15

Results Overview

According to CTCae any dose causing grade 2 or worse toxicity will be an untolerated dose. Tolerability is defined as ability to take the medication for 2 weeks without having a grade 2 or worse toxicity.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Up to 2 weeks

Results posted on

2013-02-15

Participant Flow

Recruitment began in June 2011 and closed in April 2012. Patients were referred by their primary pain physician.

Participant milestones

Participant milestones
Measure	Ketamine 0.25 mg/kg/Dose Cohort of three participants treated at 0.25 mg/kg/dose oral ketamine.	Ketamine 0.5 mg/kg/Dose Cohort of three participants treated at 0.5 mg/kg/dose oral ketamine.	Ketamine 1 mg/kg/Dose Cohort of three participants treated at 1 mg/kg/dose oral ketamine.	Ketamine 1.5 mg/kg/Dose Cohort of three participants treated at 1.5 mg/kg/dose oral ketamine.
Overall Study STARTED	3	3	3	3
Overall Study COMPLETED	3	3	2	1
Overall Study NOT COMPLETED	0	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ketamine 0.25 mg/kg/Dose Cohort of three participants treated at 0.25 mg/kg/dose oral ketamine.	Ketamine 0.5 mg/kg/Dose Cohort of three participants treated at 0.5 mg/kg/dose oral ketamine.	Ketamine 1 mg/kg/Dose Cohort of three participants treated at 1 mg/kg/dose oral ketamine.	Ketamine 1.5 mg/kg/Dose Cohort of three participants treated at 1.5 mg/kg/dose oral ketamine.
Overall Study Lost to Follow-up	0	0	1	2

Baseline Characteristics

Oral Ketamine for Control of Chronic Pain in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine 0.25 mg/kg/Dose n=3 Participants Cohort of three participants treated at 0.25 mg/kg/dose oral ketamine.	Ketamine 0.5 mg/kg/Dose n=3 Participants Cohort of three participants treated at 0.5 mg/kg/dose oral ketamine.	Ketamine 1 mg/kg/Dose n=3 Participants Cohort of three participants treated at 1 mg/kg/dose oral ketamine.	Ketamine 1.5 mg/kg/Dose n=3 Participants Cohort of three participants treated at 1.5 mg/kg/dose oral ketamine.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	11 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	12 participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 2 weeks

Population: Number of participants was determined through negotiation with the FDA for safety of all participants.

Outcome measures

Outcome measures
Measure	Ketamine 0.25 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.25 mg/kg/dose oral ketamine	Ketamine 0.5 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.5 mg/kg/dose oral ketamine	Ketamine 1 mg/kg/Dose n=3 Participants Cohort of three subjects administered 1 mg/kg/dose oral ketamine	Ketamine 1.5 mg/kg/Dose n=3 Participants Cohort of three subjects administered 1.5 mg/kg/dose oral ketamine
Number of Participants Tolerating Dose	3 participants	3 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: At 14 weeks

Population: All participants not lost to follow-up were analyzed

Baseline neurocognitive testing will be done before study drug is given. Subjects will be reassessed for any changes in neurocognitive scores at end of dosing (week 2) and at three weeks off study drug (week 14). Significant changes were measured at week 14 compared to baseline. Week 2 was measured to inform future studies. The neurocognitive scores are standardized scores with a mean of 100; low scores correlate with low neurocognitive function, while high scores correlate with high function. A significant change is defined as greater than or equal to 10% decrease in scores.

Outcome measures

Outcome measures
Measure	Ketamine 0.25 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.25 mg/kg/dose oral ketamine	Ketamine 0.5 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.5 mg/kg/dose oral ketamine	Ketamine 1 mg/kg/Dose n=2 Participants Cohort of three subjects administered 1 mg/kg/dose oral ketamine	Ketamine 1.5 mg/kg/Dose n=1 Participants Cohort of three subjects administered 1.5 mg/kg/dose oral ketamine
Neurocognitive Effect	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: At week 1

Population: All participants consenting for pharmacokinetics were analyzed. No participants in ketamine 1.5 mg/kg/dose group consented for pharmacokinetics.

Pharmacokinetic testing will be done during chronic ketamine administration on subjects consenting to additional testing one week into study drug administration. This is to further describe the activity of ketamine in the blood of children when administered chronically and to enable comparison of any clinical effect or toxicity with steady state levels of ketamine in children.

Outcome measures

Outcome measures
Measure	Ketamine 0.25 mg/kg/Dose n=2 Participants Cohort of three subjects administered 0.25 mg/kg/dose oral ketamine	Ketamine 0.5 mg/kg/Dose n=2 Participants Cohort of three subjects administered 0.5 mg/kg/dose oral ketamine	Ketamine 1 mg/kg/Dose n=1 Participants Cohort of three subjects administered 1 mg/kg/dose oral ketamine	Ketamine 1.5 mg/kg/Dose Cohort of three subjects administered 1.5 mg/kg/dose oral ketamine
Norketamine Cmax (Measured in ng/mL).	37.5 ng/mL Interval 20.0 to 55.0	135 ng/mL Interval 120.0 to 150.0	250 ng/mL Interval 250.0 to 250.0	—

SECONDARY outcome

Timeframe: Week 2

Population: Number of participants for analysis was determined in negotiation with the FDA for safety of all participants.

Subjects will be assessed for clinically significant change in pain scores during and after study drug administration. Significant change in pain scores were determined at week 2, though week 14 scores were collected as well. Participants with a 2 point (or greater) decrease in pain scores compared to baseline were considered to have responded. The NRS scale was used, the scale ranges from 0-10, with 10 being the most pain.

Outcome measures

Outcome measures
Measure	Ketamine 0.25 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.25 mg/kg/dose oral ketamine	Ketamine 0.5 mg/kg/Dose n=3 Participants Cohort of three subjects administered 0.5 mg/kg/dose oral ketamine	Ketamine 1 mg/kg/Dose n=3 Participants Cohort of three subjects administered 1 mg/kg/dose oral ketamine	Ketamine 1.5 mg/kg/Dose n=3 Participants Cohort of three subjects administered 1.5 mg/kg/dose oral ketamine
Pain Control	3 participants	0 participants	2 participants	0 participants

Adverse Events

Ketamine 0.25 mg/kg/Dose

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Ketamine 0.5 mg/kg/Dose

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Ketamine 1 mg/kg/Dose

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Ketamine 1.5 mg/kg/Dose

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ketamine 0.25 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 0.25 mg/kg/dose oral ketamine.	Ketamine 0.5 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 0.5 mg/kg/dose oral ketamine.	Ketamine 1 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 1 mg/kg/dose oral ketamine.	Ketamine 1.5 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 1.5 mg/kg/dose oral ketamine.
Infections and infestations Infection	33.3% 1/3 • Number of events 3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months
Nervous system disorders Pain	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months

Other adverse events

Other adverse events
Measure	Ketamine 0.25 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 0.25 mg/kg/dose oral ketamine.	Ketamine 0.5 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 0.5 mg/kg/dose oral ketamine.	Ketamine 1 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 1 mg/kg/dose oral ketamine.	Ketamine 1.5 mg/kg/Dose n=3 participants at risk Cohort of three participants treated at 1.5 mg/kg/dose oral ketamine.
Nervous system disorders Confusion	33.3% 1/3 • Number of events 1 • 4 months	66.7% 2/3 • Number of events 2 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	33.3% 1/3 • Number of events 1 • 4 months
General disorders Chills	33.3% 1/3 • Number of events 1 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months
Nervous system disorders Headache	0.00% 0/3 • 4 months	66.7% 2/3 • Number of events 2 • 4 months	66.7% 2/3 • Number of events 2 • 4 months	0.00% 0/3 • 4 months
Nervous system disorders Dizziness	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	66.7% 2/3 • Number of events 2 • 4 months
Nervous system disorders Pain	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	33.3% 1/3 • Number of events 1 • 4 months
Nervous system disorders Memory impairment	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months	0.00% 0/3 • 4 months
Gastrointestinal disorders Vomiting	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 4 • 4 months
Gastrointestinal disorders Anorexia	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months
General disorders Chest pain	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months
Nervous system disorders Depressed level of consciousness	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	0.00% 0/3 • 4 months	33.3% 1/3 • Number of events 1 • 4 months

Additional Information

Dr. Amy-Lee Bredlau

Medical University of South Carolina

Phone: 843-792-2957

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place