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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.
The treatment duration is 2 weeks per period. Each treatment period is followed by a one-week washout period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| THN102 Dosage A | Placebo Comparator | THN102 Dosage A is a Placebo |
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| THN102 Dosage B | Experimental | THN102 Dosage B : 200 mg/2 mg THN102 is a combination of modafinil 100mg and flecainide 1 mg daily dosage is 200 mg of modafinil and 2 mg of flecainide |
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| THN102 Dosage C | Experimental | THN102 Dosage C : 200 mg/18 mg THN102 is a combination of modafinil 100mg and flecainide 9 mg daily dosage is 200 mg of modafinil and 18 mg of flecainide |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| THN102 Dosage A | Drug | THN102 Dosages A: placebo |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety Adverse Events | Number of participants with spontaneously reported treatment-related adverse events | 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 weeks |
| Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Christophe Corvol, Prof | Hôpital La Pitié-Salpêtrière, 75651 Paris, France, Tel. +33 1 42 16 57 66, mail: jean-christophe.corvol@aphp.fr | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States | ||
| MGH Neurological Clinical Research Institute |
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105 patients were screened and 77 were randomized and allowed to start the medications periods.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | Sequence BCA |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 27, 2019 | Sep 15, 2020 |
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Complete 3 way-Crossover
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| THN102 Dosage B | Drug | THN102 Dosage B : 200mg/2mg |
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| THN102 Dosage C | Drug | THN102 Dosage C: 200mg/18mg |
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PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline. |
| 2 weeks |
| 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. | 2 weeks |
| 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 | 2 weeks |
| 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 | 2 weeks |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| I. neurologická klinika Fakultní nemocnice u sv. Anny | Brno | 65691 | Czechia |
| Neurologická klinika Fakultní nemocnice Hradec Králové | Hradec Králové | 50005 | Czechia |
| Neurologická klinika Fakultní nemocnice Ostrava | Ostrava Poruba | 70852 | Czechia |
| Neurologická klinika 1.LF UK a VFN v Praze | Prague | 12821 | Czechia |
| NEURO - Praha, s.r.o. | Prague | 14000 | Czechia |
| Axon Clinical, s.r.o. | Prague | 15030 | Czechia |
| Neurologické oddělení Nemocnice Na Homolce | Prague | 15030 | Czechia |
| Institut neuropsychiatrické péče | Prague | Czechia |
| Hôpital NEurologique Pierre Wertheimer | Bron | 69677 | France |
| CHRU Hopital Salengro | Lille | 59037 | France |
| CHU de la Timone Service de Neuro et pathologie du mouvement | Marseille | 13385 | France |
| CHRU Guy de Chauliac | Montpellier | 34195 | France |
| ICM Centre d'Investigation Clinique Hôpital Pitié Salpêtrière | Paris | 75013 | France |
| CHU Charles Nicolle | Rouen | 76031 | France |
| CHU Purpan CIC Hall D 2eme etage | Toulouse | 31059 | France |
| Praxis Dr. Safavi, Neuroakademie Alzenau | Alzenau in Unterfranken | 63755 | Germany |
| Charité - Universitätsmedizin Berlin, Klinik für Neurologie, Campus Benjamin Franklin | Berlin | 12203 | Germany |
| Neurologische Praxis Dipl. med. Christian Oehlwein | Gera | 05551 | Germany |
| Pharmakologisches Studienzentrum Chemnitz | Mittweida | 09648 | Germany |
| Technische Universität München, Klinikum rechts der Isar, Neurologische Klinik und Poliklinik, Neuro-Kopf-Zentrum | München | 81675 | Germany |
| Praxis Dr. med. Arnfin Bergmann | Neuburg am Inn | 86633 | Germany |
| Neurozentrum Sophienstrasse | Stuttgart | 70178 | Germany |
| NeuroPoint | Ulm | 89073 | Germany |
| Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West, *ausgelagerte Praxisräume: | Westerstede | 26655 | Germany |
| Nyírő Gyula Országos Pszichiátriai és Addiktológiai Intézet, Neurológiai Osztály | Budapest | 1135 | Hungary |
| Észak-Közép-budai Centrum | Budapest | Hungary |
| Debreceni Egyetem Kenézy Gyula Egyetemi Kórház Neurológiai Osztály | Debrecen | 4031 | Hungary |
| Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktató Kórház, Stroke, Vascularis és Általános Neurológiai és Toxikológiai Osztály | Miskolc | 3526 | Hungary |
| PTE KK Neurológiai Klinika | Pécs | 7623 | Hungary |
| Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ Neurológiai Klinika | Szeged | 6725 | Hungary |
| Theranexus Investigational site | Szeged | Hungary |
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) |
| FG002 | 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) |
| FG003 | 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) |
| FG004 | 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) |
| FG005 | 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) |
| COMPLETED |
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| NOT COMPLETED |
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mITT
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | 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) |
| BG002 | 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) |
| BG003 | 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) |
| BG004 | 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) |
| BG005 | 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) |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||
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| Primary | Safety Adverse Events | Number of participants with spontaneously reported treatment-related adverse events | Overall number of participant reported corresponds to the safety set population of the clinical report | Posted | Number | participants | 2 weeks |
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| 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. | modified intent to treat | Posted | Least Squares Mean | Standard Error | score on a scale | 2 weeks |
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| 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. | PVT full analysis set | Posted | Least Squares Mean | Standard Error | millisecond (msec) | 2 weeks |
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| 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. | mITT | Posted | Least Squares Mean | Standard Error | score on a scale | 2 weeks |
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| 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 | mITT | Posted | Count of Participants | Participants | 2 weeks |
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| 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 | mITT | Posted | Count of Participants | Participants | 2 weeks |
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AE collection through study duration, starts with screening until follow up visit (last phone call), a total of 13 weeks.
Listing of AEs reported are corresponding to TEAEs (treatment emergent adverse event) collected from randomization to last visit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | THN102 Placebo | THN102 Placebo (Dosage A) | 0 | 68 | 0 | 68 | 3 | 68 |
| EG001 | THN102 200/2 | THN102 200 mg/2 mg (Dosage B) | 0 | 72 | 0 | 72 | 10 | 72 |
| EG002 | THN102 200/18 | THN102 200 mg/18 mg (Dosage C) | 0 | 73 | 1 | 73 | 22 | 73 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CONTUSION | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment | wrist contusion and low back pain after fall |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Muscle spasm | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Chest pain | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Theranexus | +33680026779 | werner.rein@theranexus.fr |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 21, 2020 | Sep 15, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Race Unknown |
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| Ethnicity : Not hispanic or latino |
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| Ethnicity : Unknown |
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| Ethnicity : not reported |
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| Subjects with at least one related serious TEAE |
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| Subjects with at least one TEAE |
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| Subjects with at least one related TEAE |
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| Subjects with at least one TEAE leading to discont |
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| Subjects with at least one related TEAE leading to |
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| Subjects with at least one serious TEAE leading to |
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