Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: THN102 Dosage A; Drug: THN102 Dosage B; Drug: THN102 Dosage C

Detailed Description

The treatment duration is 2 weeks per period. Each treatment period is followed by a one-week washout period.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 65691
    • I. neurologická klinika Fakultní nemocnice u sv. Anny
  • Hradec Králové, Czechia, 50005
    • Neurologická klinika Fakultní nemocnice Hradec Králové
  • Ostrava Poruba, Czechia, 70852
    • Neurologická klinika Fakultní nemocnice Ostrava
  • Praga 8, Czechia
    • Institut neuropsychiatricke pece
  • Praha 2, Czechia, 12821
    • Neurologická klinika 1.LF UK a VFN v Praze
  • Praha 4, Czechia, 14000
    • NEURO - Praha, s.r.o.
  • Praha 5, Czechia, 15030
    • Axon Clinical, s.r.o.
  • Praha 5, Czechia, 15030
    • Neurologické oddělení Nemocnice Na Homolce
• France
  • Bron, France, 69677
    • Hopital Neurologique Pierre Wertheimer
  • Lille, France, 59037
    • CHRU Hopital Salengro
  • Marseille, France, 13385
    • CHU de la Timone Service de Neuro et pathologie du mouvement
  • Montpellier, France, 34195
    • CHRU Guy de Chauliac
  • Paris, France, 75013
    • ICM Centre d'Investigation Clinique Hôpital Pitié Salpêtrière
  • Rouen, France, 76031
    • CHU Charles Nicolle
  • Toulouse, France, 31059
    • CHU Purpan CIC Hall D 2eme etage
• Germany
  • Alzenau In Unterfranken, Germany, 63755
    • Praxis Dr. Safavi, Neuroakademie Alzenau
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin, Klinik für Neurologie, Campus Benjamin Franklin
  • Gera, Germany, 05551
    • Neurologische Praxis Dipl. med. Christian Oehlwein
  • Mittweida, Germany, 09648
    • Pharmakologisches Studienzentrum Chemnitz
  • München, Germany, 81675
    • Technische Universität München, Klinikum rechts der Isar, Neurologische Klinik und Poliklinik, Neuro-Kopf-Zentrum
  • Neuburg, Germany, 86633
    • Praxis Dr. med. Arnfin Bergmann
  • Stuttgart, Germany, 70178
    • Neurozentrum Sophienstraße
  • Ulm, Germany, 89073
    • NeuroPoint
  • Westerstede, Germany, 26655
    • Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West, *ausgelagerte Praxisräume:
• Hungary
  • Budapest, Hungary, 1135
    • Nyírő Gyula Országos Pszichiátriai és Addiktológiai Intézet, Neurológiai Osztály
  • Budapest, Hungary
    • Észak-Közép-budai Centrum
  • Debrecen, Hungary, 4031
    • Debreceni Egyetem Kenézy Gyula Egyetemi Kórház Neurológiai Osztály
  • Miskolc, Hungary, 3526
    • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktató Kórház, Stroke, Vascularis és Általános Neurológiai és Toxikológiai Osztály
  • Pécs, Hungary, 7623
    • PTE KK Neurológiai Klinika
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ Neurológiai Klinika
  • Szeged, Hungary
    • Theranexus Investigational site
• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • MGH Neurological Clinical Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: THN102 Dosage A; THN102 Dosage A is a Placebo	Drug: THN102 Dosage A; THN102 Dosages A: placebo; Other Names: Placebo
Experimental: THN102 Dosage B; 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	Drug: THN102 Dosage B; THN102 Dosage B : 200mg/2mg; Other Names: Dosage B
Experimental: THN102 Dosage C; 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	Drug: THN102 Dosage C; THN102 Dosage C: 200mg/18mg; Other Names: Dosage C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Adverse Events	Number of participants with spontaneously reported treatment-related adverse events	2 weeks

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Theranexus
• Investigators: Study Chair: 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 record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Actual): December 20, 2019
• Study Completion (Actual): February 24, 2020

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 27, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Disorders of Excessive Somnolence; Sleepiness
• Other Study ID Numbers: THN102-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No