Trial Outcomes & Findings for Driving Simulation to Assess Non-Sedative Effects of Tolperisone (NCT NCT03353922)

Last Updated: 2022-02-01

Results Overview

In this crossover study, treatment effects were assessed following initial dose, the morning following nighttime dosing (to assess residual next day effects), and at steady state (i.e., following AM dosing on Day 3).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

at time of peak concentration of drug (Tmax) on Day 1

Results posted on

2022-02-01

Participant Flow

Randomized 3-way cross-over of multiple doses of 150 mg tolperisone, 10 mg cyclobenzaprine, or placebo TID in 35 male \& female healthy volunteers. Treatment groups A (Tolperisone), B (Cyclobenzaprine), and C (Placebo) randomized by 6 treatment sequences. Subjects serve as own positive control, data analyzed and reported based on treatment type.

Participant milestones

Participant milestones
Measure	ABC (Tolperisone, Cyclobenzaprine, Placebo) 1st intervention: 150 mg tolperisone tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: placebo every 8 hours for 3 days, followed by release from clinic.	ACB (Tolperisone, Placebo, Cyclobenzaprine) 1st intervention: 150 mg tolperisone tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: placebo every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by release from clinic.	BAC (Cyclobenzaprine, Tolperisone, Placebo) 1st intervention: 10 mg cyclobenzaprine tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 150 mg tolperisone cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: placebo every 8 hours for 3 days, followed by release from clinic.	BCA (Cyclobenzaprine, Placebo, Tolperisone) 1st intervention: 10 mg cyclobenzaprine tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: placebo every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by release from clinic.	CAB (Placebo, Tolperisone, Cyclobenzaprine) 1st intervention: placebo tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by release from clinic.	CBA (Placebo, Cyclobenzaprine, Tolperisone) 1st intervention: placebo tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by release from clinic.
Overall Study STARTED	6	6	6	6	5	6
Overall Study COMPLETED	5	5	5	5	5	6
Overall Study NOT COMPLETED	1	1	1	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ABC (Tolperisone, Cyclobenzaprine, Placebo) 1st intervention: 150 mg tolperisone tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: placebo every 8 hours for 3 days, followed by release from clinic.	ACB (Tolperisone, Placebo, Cyclobenzaprine) 1st intervention: 150 mg tolperisone tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: placebo every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by release from clinic.	BAC (Cyclobenzaprine, Tolperisone, Placebo) 1st intervention: 10 mg cyclobenzaprine tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 150 mg tolperisone cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: placebo every 8 hours for 3 days, followed by release from clinic.	BCA (Cyclobenzaprine, Placebo, Tolperisone) 1st intervention: 10 mg cyclobenzaprine tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: placebo every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by release from clinic.	CAB (Placebo, Tolperisone, Cyclobenzaprine) 1st intervention: placebo tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by release from clinic.	CBA (Placebo, Cyclobenzaprine, Tolperisone) 1st intervention: placebo tablets administered every 8 hours for 3 days, followed by washout period of 4 days, then 2nd intervention: 10 mg cyclobenzaprine every 8 hours for 3 days, followed by 4 day washout, then 3rd intervention: 150 mg tolperisone every 8 hours for 3 days, followed by release from clinic.
Overall Study Withdrawal by Subject	1	0	1	1	0	0
Overall Study Adverse Event	0	1	0	0	0	0

Baseline Characteristics

Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=33 Participants All Study Participants; n=33
Age, Categorical <=18 years	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Age, Categorical >=65 years	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Sex: Female, Male Female	10 Participants n=5 Participants • Cross over design for subjects, not independent groups
Sex: Female, Male Male	23 Participants n=5 Participants • Cross over design for subjects, not independent groups
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) Asian	1 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) White	17 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed
BMI	25.012 kg/m2 STANDARD_DEVIATION 2.959 • n=5 Participants • Final analysis on per protocol population (n=33) instead of ITT (n=35) due to 2 subjects being mis-dosed

PRIMARY outcome

Timeframe: at time of peak concentration of drug (Tmax) on Day 1

Population: per protocol

Outcome measures

Outcome measures
Measure	Tolperisone HCl 150 mg n=33 Participants 150 mg tolperisone tablets administered by mouth every 8 hours for 3 days	Placebo Oral Tablet n=31 Participants sugar pills administered by mouth every 8 hours for 3 days	Cyclobenzaprine 10 mg Oral Tablet n=33 Participants 10 mg cyclobenzapine tablets administered by mouth every 8 hours for 3 days
Standard Deviation of Lateral Position (SDLP)	29.3 cm of deviation of lateral position Standard Deviation 6.25	29.7 cm of deviation of lateral position Standard Deviation 6.37	38.6 cm of deviation of lateral position Standard Deviation 12.35

SECONDARY outcome

Timeframe: in the morning predose on Day 2 following nighttime dosing

Population: Per protocol population was analyzed per treatment group, therefore all subjects completing a treatment were included in the analysis

SDLP measured by simulated driving performance of tolperisone compared to placebo on Day 2 prior to morning dosing to determine the next day residual effect or hangover of treatment

Outcome measures

Outcome measures
Measure	Tolperisone HCl 150 mg n=33 Participants 150 mg tolperisone tablets administered by mouth every 8 hours for 3 days	Placebo Oral Tablet n=31 Participants sugar pills administered by mouth every 8 hours for 3 days	Cyclobenzaprine 10 mg Oral Tablet n=33 Participants 10 mg cyclobenzapine tablets administered by mouth every 8 hours for 3 days
Standard Deviation of Lateral Position (SDLP) in Simulated Driving Test of Tolperisone Compared to Placebo on Day 2 Next Day Residual Effect	29.6 cm of deviation from lateral position Standard Deviation 7.08	29.9 cm of deviation from lateral position Standard Deviation 7.71	35.1 cm of deviation from lateral position Standard Deviation 10.37

SECONDARY outcome

Timeframe: at Tmax on Day 1

Population: per protocol

assessment of self-reported motivation for driving performance where 1 equals alert and 9 equals extremely sleepy

Outcome measures

Outcome measures
Measure	Tolperisone HCl 150 mg n=29 Participants 150 mg tolperisone tablets administered by mouth every 8 hours for 3 days	Placebo Oral Tablet n=31 Participants sugar pills administered by mouth every 8 hours for 3 days	Cyclobenzaprine 10 mg Oral Tablet n=31 Participants 10 mg cyclobenzapine tablets administered by mouth every 8 hours for 3 days
Sleepiness Endpoint Karolinska Sleepiness Scale KSS	3.3 units on a scale Standard Deviation 1.96	3.4 units on a scale Standard Deviation 1.99	5.6 units on a scale Standard Deviation 2.44

SECONDARY outcome

Timeframe: Day 3

Population: ITT

SDLP measured on Day 3 at steady state following 3 days of dosing three times per day to achieve steady state drug concentration and effect on outcomes

Outcome measures

Outcome measures
Measure	Tolperisone HCl 150 mg n=29 Participants 150 mg tolperisone tablets administered by mouth every 8 hours for 3 days	Placebo Oral Tablet n=31 Participants sugar pills administered by mouth every 8 hours for 3 days	Cyclobenzaprine 10 mg Oral Tablet n=31 Participants 10 mg cyclobenzapine tablets administered by mouth every 8 hours for 3 days
Steady State Standard Deviation of Lateral Position (SDLP) Day 3	29.8 cm deviation from lateral position Standard Deviation 6.68	29.6 cm deviation from lateral position Standard Deviation 7.46	31.7 cm deviation from lateral position Standard Deviation 7.9

Adverse Events

Tolperisone HCl 150 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo Oral Tablet

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Cyclobenzaprine 10 mg Oral Tablet

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Judy Caron, Chief Operating Officer

Neurana Pharmaceuticals

Phone: (617) 640-5043

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Tolperisone HCl 150 mg n=33 participants at risk 150 mg tolperisone tablets administered by mouth every 8 hours for 3 days	Placebo Oral Tablet n=31 participants at risk sugar pills administered by mouth every 8 hours for 3 days	Cyclobenzaprine 10 mg Oral Tablet n=33 participants at risk 10 mg cyclobenzapine tablets administered by mouth every 8 hours for 3 days
Nervous system disorders dizziness	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	6.5% 2/31 • Number of events 2 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	9.1% 3/33 • Number of events 3 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Nervous system disorders headache	6.1% 2/33 • Number of events 2 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Nervous system disorders somnolence	15.2% 5/33 • Number of events 5 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	6.5% 2/31 • Number of events 2 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	30.3% 10/33 • Number of events 10 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders dry mouth	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	6.1% 2/33 • Number of events 2 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders abdominal pain	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders Crohn's disease	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders nausea	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	6.5% 2/31 • Number of events 2 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders dyspepsia	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Gastrointestinal disorders frequent bowel movement	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Eye disorders vision blurred	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
General disorders sluggishness	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Infections and infestations upper respiratory infection	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Cardiac disorders tachycardia	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Injury, poisoning and procedural complications road traffic accident	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Psychiatric disorders insomnia	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Respiratory, thoracic and mediastinal disorders dry throat	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Skin and subcutaneous tissue disorders hyperhydrosis	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Respiratory, thoracic and mediastinal disorders skin exfoliation	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.2% 1/31 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Nervous system disorders lethargy	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.
Nervous system disorders disturbance inattention	3.0% 1/33 • Number of events 1 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/31 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.	0.00% 0/33 • The total duration of study participation was approximately 4 weeks including screening to follow up. No difference in definition.