Trial Outcomes & Findings for Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI) (NCT NCT01058395)

Last Updated: 2018-09-17

Results Overview

The main outcome measure after the safety data was the Disability Rating Scale (DRS). It is a 29 point scale with 29 being a severe vegetative state. It is reliable across time and demonstrates better sensitivity than the Glasgow Outcome Scale.It has been a standard primary outcome measure for most pharmaceutical studies for TBI, and was required by the FDA for the IND approval.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

4 weeks and 3 months

Results posted on

2018-09-17

Participant Flow

Participant milestones

Participant milestones
Measure	800 mg Loading Then 200 mg Q12 Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Overall Study STARTED	7	8
Overall Study COMPLETED	4	7
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	800 mg Loading Then 200 mg Q12 Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Overall Study Death	2	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	800 mg Loading Then 200 mg Q12 n=7 Participants Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 n=8 Participants Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	46 years n=5 Participants	40 years n=7 Participants	43 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks and 3 months

Outcome measures

Outcome measures
Measure	800 mg Loading Then 200 mg Q12 n=4 Participants Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 n=7 Participants Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Disability Rating Scale DRS at 4 weeks	12.5 units on a scale Standard Deviation 7.7	9.7 units on a scale Standard Deviation 6.9
Disability Rating Scale DRS at 3 months	8.5 units on a scale Standard Deviation 9.9	6.0 units on a scale Standard Deviation 6.1

SECONDARY outcome

Timeframe: 4 days after start

Population: Those we were able to obtain levels on reliably and could run against standards. This only turned out to be the first tier level. Descriptive data only

Serum samples were collected for assessment of minocycline concentrations at the estimated time of steady-state concentrations. Serum concentrations were assessed on Day 4. Data reported will be pKa levels 2 hours after AM dose.

Outcome measures

Outcome measures
Measure	800 mg Loading Then 200 mg Q12 n=4 Participants Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Drug Levels	21.7 mcg/ml Interval 6.2 to 61.3	—

POST_HOC outcome

Timeframe: day 1 change to day 7 day, ANOVA, mean value on day 7 reported

Population: Levels are compared for the two tiers

AST levels measured daily from day 1 to day 7 evaluated by ANOVA. Mean values on day 7 reported for the two tiers. Elevations may indicate Liver dysfunction due to medication.

Outcome measures

Outcome measures
Measure	800 mg Loading Then 200 mg Q12 n=4 Participants Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 n=7 Participants Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Aspartate Aminotransferase (AST) Levels	88.0 U/L Interval 31.0 to 245.0	264 U/L Interval 30.0 to 1092.0

Adverse Events

800 mg Loading Then 200 mg Q12

Serious events: 0 serious events

Other events: 7 other events

Deaths: 2 deaths

800 mg Loading Then 400 mg Q12

Serious events: 0 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	800 mg Loading Then 200 mg Q12 n=7 participants at risk Minocycline 800 mg. loading followed by 200 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.	800 mg Loading Then 400 mg Q12 n=8 participants at risk Minocycline 800 mg. loading followed by 400 mg. Q 12 hours. Minocycline: Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Nervous system disorders Medical	100.0% 7/7 • 3 months Serious Adverse l event medical or laboratory related to the use of the medication.	100.0% 8/8 • 3 months Serious Adverse l event medical or laboratory related to the use of the medication.

Additional Information

Dr. Jay Meythaler

Wayne State University

Phone: (313) 375-7226

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place