Parkinson Disease
Conditions
Brief summary
This is a randomized, placebo-controlled, 3-way cross-over phase IIa trial comparing two dose levels of THN102 to placebo in patients suffering from Parkinson's disease associated with excessive daytime sleepiness.
Detailed description
The treatment duration is 2 weeks per period. Each treatment period is followed by a one-week washout period.
Interventions
DRUGTHN102 Dosage A
THN102 Dosages A: placebo
DRUGTHN102 Dosage B
THN102 Dosage B : 200mg/2mg
DRUGTHN102 Dosage C
THN102 Dosage C: 200mg/18mg
Sponsors
Theranexus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Complete 3 way-Crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of idiopathic Parkinson's disease as defined by the Movement Disorders Society (MDS). * Subjects with Hoehn and Yahr scale score ≤ 4. * Body mass index \> 18 kg/m2 and \< 35 kg/m2. * Subjects should have a complaint of daytime sleepiness impacting their quality of life and/or daytime functioning (e.g. falling asleep while reading or watching television, while eating or talking with other people). * Epworth Sleepiness Scale (ESS) score ≥ 14.
Exclusion criteria
* Subjects with known or with a suspected sleep apnea syndrome or who have any other cause of excessive daytime sleepiness, such as shift work sleep disorder. * Psychiatric and neurological disorders (other than Parkinson's disease), * Cardiovascular disorders such as - but not limited to * Uncontrolled moderate to severe hypertension * History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study * Recent myocardial infarction * Stable or unstable angina pectoris * Cardiac insufficiency or history of heart failure * Previous history of cardiac valvular surgery * Subjects with current impulse control disorder. * Subjects showing dementia or with MoCA \< 23. * Subjects with current suicidal risk * Current or recent (within one year) history of substance abuse or dependence disorder * Other active clinically significant illness * Subjects with hepatic or renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Adverse Events | 2 weeks | Number of participants with spontaneously reported treatment-related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleeping Scale (ESS) | 2 weeks | Range of the scale : 0 to 24. A low score indicates a good outcome. Results shown are corresponding to a change from baseline of the ESS score. |
| Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline | 2 weeks | PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline. |
| Montreal Cognitive Assessment Battery (MoCA) | 2 weeks | MoCA score reflects the cognitive capacities of a person. Range of the total score of 10 test items: 0 to 30 points. A high score indicates good cognitive functioning. A score of 26 and above is considered normal. The results below are shown as change from baseline of the MoCA score. |
| Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline | 2 weeks | ESS score responder rate, defined as the proportion of subjects with at least 25% ESS improvement from baseline, at the end of each treatment period |
| Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline | 2 weeks | Number of patients in remission (=without residual sleepiness), i.e. ESS \< 11 at the end of each treatment period |
Countries
Czechia, France, Germany, Hungary, United States
Participant flow
Recruitment details
105 patients were screened and 77 were randomized and allowed to start the medications periods.
Participants by arm
| Arm | Count |
|---|---|
| Sequence ABC A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 13 |
| Sequence BCA A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 13 |
| Sequence CAB A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 13 |
| Sequence ACB A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 13 |
| Sequence CBA A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 9 |
| Sequence BAC A : 2 weeks under Placebo
B : 2 weeks under THN102 200/2 (200mg modafinil and 2 mg of flecainide per os daily)
C : 2 weeks under THN102 200/18 (200mg modafinil and 18 mg of flecainide per os daily) | 11 |
| Total | 72 |
Baseline characteristics
| Characteristic | Sequence ABC | Sequence BCA | Sequence CAB | Sequence ACB | Sequence CBA | Sequence BAC | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 7 Participants | 6 Participants | 4 Participants | 5 Participants | 8 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 7 Participants | 9 Participants | 4 Participants | 3 Participants | 34 Participants |
| Race/Ethnicity, Customized Ethnicity : Not hispanic or latino | 13 Participants | 12 Participants | 12 Participants | 13 Participants | 8 Participants | 11 Participants | 69 Participants |
| Race/Ethnicity, Customized Ethnicity : not reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity : Unknown | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race : White | 13 Participants | 13 Participants | 12 Participants | 13 Participants | 9 Participants | 11 Participants | 71 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 9 Participants | 9 Participants | 7 Participants | 9 Participants | 48 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 72 | 0 / 73 |
| other Total, other adverse events | 3 / 68 | 10 / 72 | 22 / 73 |
| serious Total, serious adverse events | 0 / 68 | 0 / 72 | 1 / 73 |
Outcome results
Primary
Safety Adverse Events
Number of participants with spontaneously reported treatment-related adverse events
Time frame: 2 weeks
Population: Overall number of participant reported corresponds to the safety set population of the clinical report
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety Adverse Events | Subjects with at least one TEAE leading to death | 0 participants |
| Placebo | Safety Adverse Events | Subject with at least one serious TEAE | 0 participants |
| Placebo | Safety Adverse Events | Subjects with at least one related serious TEAE | 0 participants |
| Placebo | Safety Adverse Events | Subjects with at least one TEAE | 19 participants |
| Placebo | Safety Adverse Events | Subjects with at least one related TEAE | 5 participants |
| Placebo | Safety Adverse Events | Subjects with at least one TEAE leading to discont | 0 participants |
| Placebo | Safety Adverse Events | Subjects with at least one related TEAE leading to | 0 participants |
| Placebo | Safety Adverse Events | Subjects with at least one serious TEAE leading to | 0 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one related serious TEAE | 0 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one related TEAE leading to | 2 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one TEAE | 23 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one related TEAE | 11 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one TEAE leading to discont | 3 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one TEAE leading to death | 0 participants |
| THN102 200/2 | Safety Adverse Events | Subject with at least one serious TEAE | 0 participants |
| THN102 200/2 | Safety Adverse Events | Subjects with at least one serious TEAE leading to | 0 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one related serious TEAE | 0 participants |
| THN102 200/18 | Safety Adverse Events | Subject with at least one serious TEAE | 1 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one TEAE leading to death | 0 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one TEAE | 29 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one related TEAE leading to | 3 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one TEAE leading to discont | 3 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one related TEAE | 18 participants |
| THN102 200/18 | Safety Adverse Events | Subjects with at least one serious TEAE leading to | 0 participants |
Secondary
Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline
Number of patients in remission (=without residual sleepiness), i.e. ESS \< 11 at the end of each treatment period
Time frame: 2 weeks
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline | 11 Participants |
| THN102 200/2 | Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline | 19 Participants |
| THN102 200/18 | Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline | 18 Participants |
Secondary
Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline
ESS score responder rate, defined as the proportion of subjects with at least 25% ESS improvement from baseline, at the end of each treatment period
Time frame: 2 weeks
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline | 19 Participants |
| THN102 200/2 | Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline | 28 Participants |
| THN102 200/18 | Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline | 25 Participants |
Secondary
Epworth Sleeping Scale (ESS)
Range of the scale : 0 to 24. A low score indicates a good outcome. Results shown are corresponding to a change from baseline of the ESS score.
Time frame: 2 weeks
Population: modified intent to treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Epworth Sleeping Scale (ESS) | -2.4422 score on a scale | Standard Error 0.5117 |
| THN102 200/2 | Epworth Sleeping Scale (ESS) | -3.8417 score on a scale | Standard Error 0.5086 |
| THN102 200/18 | Epworth Sleeping Scale (ESS) | -3.1850 score on a scale | Standard Error 0.4982 |
Secondary
Montreal Cognitive Assessment Battery (MoCA)
MoCA score reflects the cognitive capacities of a person. Range of the total score of 10 test items: 0 to 30 points. A high score indicates good cognitive functioning. A score of 26 and above is considered normal. The results below are shown as change from baseline of the MoCA score.
Time frame: 2 weeks
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Montreal Cognitive Assessment Battery (MoCA) | 0.2240 score on a scale | Standard Error 0.1935 |
| THN102 200/2 | Montreal Cognitive Assessment Battery (MoCA) | 0.03267 score on a scale | Standard Error 0.1923 |
| THN102 200/18 | Montreal Cognitive Assessment Battery (MoCA) | 0.4251 score on a scale | Standard Error 0.19 |
Secondary
Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline
PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline.
Time frame: 2 weeks
Population: PVT full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline | -21.2201 millisecond (msec) | Standard Error 10.0565 |
| THN102 200/2 | Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline | -24.1089 millisecond (msec) | Standard Error 9.9393 |
| THN102 200/18 | Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline | -19.6450 millisecond (msec) | Standard Error 9.8847 |