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

• Sponsor: Theranexus (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03624920
• Collaborator: (none)
• Enrollment: 77
• Locations: 34
• Arms: 3
• Actual Duration (Months): 19.4
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: THN102 Dosage A; Drug: THN102 Dosage B; Drug: THN102 Dosage C	Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Complete 3 way-CrossoverComplete 3 way-Crossover
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness
• Actual Study Start Date: Jul 12, 2018
• Actual Primary Completion Date: Dec 20, 2019
• Actual Study Completion Date: Feb 24, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety Adverse Events [2 weeks]

   Number of participants with spontaneously reported treatment-related adverse events

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Theranexus

Investigators

• Study Chair: Jean-Christophe Corvol, Prof, Hôpital La Pitié-Salpêtrière, 75651 Paris, France, Tel. [phone], mail: [e-mail]

Study Documents (Full-Text)

• Study Protocol - Feb 27, 2019
• Statistical Analysis Plan - Feb 21, 2020

More Information

Publications

None provided.

• Responsible Party: Theranexus
• ClinicalTrials.gov Identifier: NCT03624920
• Other Study ID Numbers: THN102-202
• First Posted: Aug 10, 2018
• Last Update Posted: Dec 1, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Parkinson Disease; Disorders of Excessive Somnolence; Sleepiness

Study Results

Participant Flow

Recruitment Details	105 patients were screened and 77 were randomized and allowed to start the medications periods.

Arm/Group Title	Sequence ABC	Sequence BCA	Sequence CAB	Sequence ACB	Sequence CBA	Sequence BAC
Arm/Group Description	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)	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)	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)	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)	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)	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)
Period Title: Overall Study
STARTED	14	14	13	13	11	12
COMPLETED	13	12	12	12	7	11
NOT COMPLETED	1	2	1	1	4	1

Baseline Characteristics

Arm/Group Title	Sequence ABC	Sequence BCA	Sequence CAB	Sequence ACB	Sequence CBA	Sequence BAC	Total
Arm/Group Description	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)	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)	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)	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)	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)	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)	Total of all reporting groups
Overall Participants	13	13	13	13	9	11	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 38.5%	6 46.2%	7 53.8%	9 69.2%	4 44.4%	3 27.3%	34 47.2%
>=65 years	8 61.5%	7 53.8%	6 46.2%	4 30.8%	5 55.6%	8 72.7%	38 52.8%
Sex: Female, Male (Count of Participants)
Female	8 61.5%	6 46.2%	9 69.2%	9 69.2%	7 77.8%	9 81.8%	48 66.7%
Male	5 38.5%	7 53.8%	4 30.8%	4 30.8%	2 22.2%	2 18.2%	24 33.3%
Race/Ethnicity, Customized (Count of Participants)
Race : White	13 100%	13 100%	12 92.3%	13 100%	9 100%	11 100%	71 98.6%
Race Unknown	0 0%	0 0%	1 7.7%	0 0%	0 0%	0 0%	1 1.4%
Ethnicity : Not hispanic or latino	13 100%	12 92.3%	12 92.3%	13 100%	8 88.9%	11 100%	69 95.8%
Ethnicity : Unknown	0 0%	0 0%	1 7.7%	0 0%	0 0%	0 0%	1 1.4%
Ethnicity : not reported	0 0%	1 7.7%	0 0%	0 0%	1 11.1%	0 0%	2 2.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Overall number of participant reported corresponds to the safety set population of the clinical report

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	72	73
Subjects with at least one TEAE leading to death	0 0%	0 0%	0 0%
Subject with at least one serious TEAE	0 0%	0 0%	1 7.7%
Subjects with at least one related serious TEAE	0 0%	0 0%	0 0%
Subjects with at least one TEAE	19 146.2%	23 176.9%	29 223.1%
Subjects with at least one related TEAE	5 38.5%	11 84.6%	18 138.5%
Subjects with at least one TEAE leading to discont	0 0%	3 23.1%	3 23.1%
Subjects with at least one related TEAE leading to	0 0%	2 15.4%	3 23.1%
Subjects with at least one serious TEAE leading to	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Epworth Sleeping Scale (ESS)
Description	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

Outcome Measure Data

Analysis Population Description

modified intent to treat

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	70	72
Least Squares Mean (Standard Error) [score on a scale]	-2.4422 (0.5117)	-3.8417 (0.5086)	-3.1850 (0.4982)

3. Secondary Outcome

Title	Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline
Description	PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

PVT full analysis set

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	70	72
Least Squares Mean (Standard Error) [millisecond (msec)]	-21.2201 (10.0565)	-24.1089 (9.9393)	-19.6450 (9.8847)

4. Secondary Outcome

Title	Montreal Cognitive Assessment Battery (MoCA)
Description	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

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	70	72
Least Squares Mean (Standard Error) [score on a scale]	0.2240 (0.1935)	0.03267 (0.1923)	0.4251 (0.1900)

5. Secondary Outcome

Title	Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	69	71
Count of Participants [Participants]	19 146.2%	28 215.4%	25 192.3%

6. Secondary Outcome

Title	Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline
Description	Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	THN102 200/2	THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)	THN102 200 mg/2 mg (Dosage B)	THN102 200 mg/18 mg (Dosage C)
Measure Participants	68	69	71
Count of Participants [Participants]	11 84.6%	19 146.2%	18 138.5%

Adverse Events

Time Frame	AE collection through study duration, starts with screening until follow up visit (last phone call), a total of 13 weeks.
Adverse Event Reporting Description	Listing of AEs reported are corresponding to TEAEs (treatment emergent adverse event) collected from randomization to last visit
Arm/Group Title	THN102 Placebo		THN102 200/2		THN102 200/18
Arm/Group Description	THN102 Placebo (Dosage A)		THN102 200 mg/2 mg (Dosage B)		THN102 200 mg/18 mg (Dosage C)
All Cause Mortality
	THN102 Placebo		THN102 200/2		THN102 200/18
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/72 (0%)		0/73 (0%)
Serious Adverse Events
	THN102 Placebo		THN102 200/2		THN102 200/18
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/72 (0%)		1/73 (1.4%)
Injury, poisoning and procedural complications
CONTUSION	0/68 (0%)	0	0/72 (0%)	0	1/73 (1.4%)	2
Other (Not Including Serious) Adverse Events
	THN102 Placebo		THN102 200/2		THN102 200/18
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)		10/72 (13.9%)		22/73 (30.1%)
Gastrointestinal disorders
Nausea	0/68 (0%)	0	2/72 (2.8%)	2	3/73 (4.1%)	3
Dry mouth	0/68 (0%)	0	0/72 (0%)	0	3/73 (4.1%)	3
General disorders
Fatigue	2/68 (2.9%)	2	0/72 (0%)	0	2/73 (2.7%)	2
Chest pain	1/68 (1.5%)	1	2/72 (2.8%)	2	1/73 (1.4%)	2
Infections and infestations
Nasopharyngitis	0/68 (0%)	0	1/72 (1.4%)	1	3/73 (4.1%)	3
Musculoskeletal and connective tissue disorders
Muscle spasm	0/68 (0%)	0	2/72 (2.8%)	2	0/73 (0%)	0
Nervous system disorders
Headache	0/68 (0%)	0	2/72 (2.8%)	2	4/73 (5.5%)	4
Psychiatric disorders
Insomnia	0/68 (0%)	0	1/72 (1.4%)	1	2/73 (2.7%)	2
Confusional state	0/68 (0%)	0	0/72 (0%)	0	2/73 (2.7%)	2
Nightmare	0/68 (0%)	0	0/72 (0%)	0	2/73 (2.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.