Download PDF

Clinical Trial Results:
A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg Twice-Daily versus Placebo for Symptomatic Treatment in Patients with Huntington’s Disease

Summary
EudraCT number	2013-001888-23
Trial protocol	DE IT NL AT PL DK
Global end of trial date	07 Jul 2016

Results information
Results version number	v1
This version publication date	09 Mar 2018
First version publication date	09 Mar 2018
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

TV7820-CNS-20002

ISRCTN number

US NCT number

NCT02006472

WHO universal trial number (UTN)

Other trial identifiers

Sponsor study acronym: PRIDE-HD

Sponsor organisation name

Teva Branded Pharmaceutical Products R&D, Inc

Sponsor organisation address

41 Moores Road, Frazer, Pennsylvania, United States, 19355

Public contact

Global Head Clinical Development, Neurodegenerative Diseases, Teva Branded Pharmaceuticals Products R&D, Inc., 001 215-591-3000, info.era-clinical@teva.de

Scientific contact

Global Head Clinical Development, Neurodegenerative Diseases, Teva Branded Pharmaceuticals Products R&D, Inc., 001 215-591-3000, info.era-clinical@teva.de

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

08 Aug 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Jul 2016

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of pridopidine 67.5 to 112.5 mg twice daily(bid) on motor impairment in patients with Huntington’s Disease (HD) after 26 weeks of treatment using the Unified Huntington’s Disease Rating Scale Total Motor Score (TMS).

Protection of trial subjects

This study was conducted in full accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations Title 21, Parts 50, 54, 56, 312, and 314; European Union (EU) Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use). Written and/or oral information about the study was provided to all patients in a language understandable by the patients. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each patient before any study procedures or assessments were done. It was explained to the patients that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment. Each patient’s willingness to participate in the study was documented in writing in a consent form that was signed by the patient with the date of that signature indicated. Each investigator kept the original consent forms, and copies were given to the patients.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Feb 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

7 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 16

Country: Number of subjects enrolled

Poland: 50

Country: Number of subjects enrolled

United Kingdom: 39

Country: Number of subjects enrolled

Austria: 27

Country: Number of subjects enrolled

Denmark: 2

Country: Number of subjects enrolled

France: 26

Country: Number of subjects enrolled

Germany: 46

Country: Number of subjects enrolled

Italy: 56

Country: Number of subjects enrolled

Australia: 14

Country: Number of subjects enrolled

Canada: 23

Country: Number of subjects enrolled

Russian Federation: 46

Country: Number of subjects enrolled

United States: 63

Worldwide total number of subjects

408

EEA total number of subjects

262

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

360

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

A total of 492 patients were screened for enrollment; 408 patients at 53 centers in Australia, Austria, Canada, Denmark, France, Germany, Italy, the Netherlands, Poland, Russia, the United Kingdom, and the US met entry criteria

Period 1 title

Treatment Period #1 (Week 26)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Randomization was performed by IRT using dynamic randomization to balance the treatment groups within centers and neuroleptics use or no use. Patients were randomly and equally assigned to the 5 treatment groups of the study (4 active treatment groups and placebo, allocation ratio of 1:1:1:1:1). All of the roles listed were blinded until the database was locked for analysis after the first 26-week study period.

Are arms mutually exclusive

Yes

Placebo

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned treatment. Patients in the Placebo arm were only supplied placebo capsules which were taken from Day 1 to Week 26 in Period 1.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Pridopidine 45 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 26 (Period 1).

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 67.5 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 26 (Period 1).

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 90 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 26 (Period 1).

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 112.5 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 26 (Period 1).

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Number of subjects in period 1	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Started	82	81	82	81	82
Completed	70	59	65	67	62
Not completed	12	22	17	14	20
Consent withdrawn by subject	3	9	3	-	3
Adverse event, non-fatal	5	6	11	11	14
Not specified	1	5	-	2	3
Non-compliance	2	1	1	-	-
Protocol deviation	1	1	1	1	-
Lack of efficacy	-	-	1	-	-

Period 2 title

Treatment Period #2 (Week 52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Blinding implementation details

After the data base was cleaned and locked for the analysis of the first 26-week study period and treatment assignment were revealed, select sponsor personnel had access to treatment assignments. The sponsor study core team were only exposed to data summaries by treatments. Investigators, the patient, and any other personnel involved in patients’ assessment, monitoring, analysis and data management were blinded to patient assignment until the database was locked for analysis of week 52 data.

Are arms mutually exclusive

Yes

Placebo

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned treatment. Patients assigned to the Placebo arm were supplied only placebo capsules which were taken from Day 1 to week 26 in Period 1, and then continued to week 52 in Period 2.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Pridopidine 45 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 26 (Period 1) and then continued to week 52 in Period 2.

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 67.5 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 26 (Period 1), and continued to Week 52 in Period 2.

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 90 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 26 (Period 1) and continued up to Week 52 in Period 2.

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Pridopidine 112.5 mg bid

Arm description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 26 (Period 1), continuing up to Week 52 in Period 2.

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo was presented as white, hard gelatin capsules matching the 22.5 mg or 45 mg pridopidine capsules but containing no active ingredient.

Investigational medicinal product name

pridopidine

Investigational medicinal product code

Other name

pridopidine hydrochloride, TV-7820

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Pridopidine was presented as white, hard gelatin capsules of 22.5 mg or 45 mg.

Number of subjects in period 2 ^[1]	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Started	57	49	54	56	46
Completed	52	43	44	53	44
Not completed	5	6	10	3	2
Adverse event, serious fatal	-	-	-	1	1
Consent withdrawn by subject	2	1	2	-	-
Adverse event, non-fatal	1	4	5	-	-
Not specified	-	1	-	1	-
Non-compliance	1	-	-	-	-
Did not receive study drug	-	-	2	-	-
Sponsor decision	-	-	1	-	-
Lack of efficacy	1	-	-	1	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Sixty-one participants completed treatment period 1 but did not continue into treatment period 2. These patients were lost due to prolonged IRB review periods at certain sites.

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Pridopidine 45 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 67.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 90 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 112.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group values	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid	Total
Number of subjects	82	81	82	81	82	408
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	50.3 ± 11.34	51.9 ± 11.75	51.0 ± 11.83	51.3 ± 12.69	47.5 ± 11.40	-
Gender categorical
Units: Subjects
Female	40	40	41	43	39	203
Male	42	41	41	38	43	205
Race
Units: Subjects
White	73	75	78	75	77	378
Black	0	0	1	0	0	1
Asian	1	0	0	1	0	2
Other	0	1	0	1	0	2
Missing	8	5	3	4	5	25
Ethnicity
Units: Subjects
Not Hispanic or Latino	71	73	76	76	75	371
Hispanic or Latino	3	3	3	0	2	11
Unknown	0	0	0	1	0	1
Missing	8	5	3	4	5	25
Use of Neuroleptics
Antipsychotic drugs to treat psychiatric or behavioral problems associated with HD.
Units: Subjects
Neuroleptics use	31	31	32	31	32	157
Neuroleptics no use	51	50	50	50	50	251
CYP2D6 Genotype
CYP2D6 is an enzyme. An association between CYP2D6 genotypes (genetic make-up) and phenotypes (response to treatment, specifically rate of metabolism of the drug) is believed to exist.
Units: Subjects
Poor	1	5	4	2	4	16
Extensive	72	70	70	74	69	355
Intermediate	8	5	8	5	9	35
Ultra-rapid	1	1	0	0	0	2
Weight
Units: kg
arithmetic mean (standard deviation)	72.7 ± 1.36	69.5 ± 1.55	69.9 ± 12.76	70.5 ± 11.83	70.7 ± 14.60	-
Height
Units: cm
arithmetic mean (standard deviation)	171.2 ± 9.77	170.5 ± 9.70	168.9 ± 9.77	169.8 ± 10.03	170.5 ± 9.22	-
Body Mass Index
Units: kg/m^2
arithmetic mean (standard deviation)	24.9 ± 4.38	23.8 ± 3.78	24.5 ± 3.93	24.4 ± 3.63	24.2 ± 3.89	-
Number of Cytosine-Adenosine-Guanine (CAG) Repeats
The normal huntington protein contains multiple repeats of a sequence of three DNA bases, cytosine-adenine-guanine (CAG), which encodes the amino acid glutamine. When more than 36 repeats are present in the protein, stemming from a mutation in the huntingtin gene, an abnormal protein is produced. This mutant form of the protein is more prone to aggregation than versions of the protein with a normal number of repeats. Individuals with 36–40 CAG repeats may or may not develop symptoms of HD, while people with more than 40 repeats will develop the disorder during a normal lifetime.
Units: repeats
arithmetic mean (standard deviation)	44.4 ± 3.23	44.1 ± 4.12	45.0 ± 4.73	44.5 ± 4.90	45.3 ± 3.66	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Pridopidine 45 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 67.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 90 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Pridopidine 112.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 26 (Period 1).

Reporting group title

Placebo

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned treatment. Patients assigned to the Placebo arm were supplied only placebo capsules which were taken from Day 1 to week 26 in Period 1, and then continued to week 52 in Period 2.

Reporting group title

Pridopidine 45 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 26 (Period 1) and then continued to week 52 in Period 2.

Reporting group title

Pridopidine 67.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 26 (Period 1), and continued to Week 52 in Period 2.

Reporting group title

Pridopidine 90 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 26 (Period 1) and continued up to Week 52 in Period 2.

Reporting group title

Pridopidine 112.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 26 (Period 1), continuing up to Week 52 in Period 2.

Subject analysis set title

Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Pridopidine 45 mg bid

Subject analysis set type

Safety analysis

Subject analysis set description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 52.

Subject analysis set title

Pridopidine 67.5 mg bid

Subject analysis set type

Safety analysis

Subject analysis set description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 52.

Subject analysis set title

Pridopidine 90 mg bid

Subject analysis set type

Safety analysis

Subject analysis set description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 52.

Subject analysis set title

Pridopidine 112.5 mg bid

Subject analysis set type

Safety analysis

Subject analysis set description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 52.

Primary: Change from Baseline in Total Motor Score (TMS) at Week 26

Top of page

End point title

Change from Baseline in Total Motor Score (TMS) at Week 26

End point description

TMS was defined as the sum of all Unified Huntington's Disease Rating Scale (UHDRS) motor domains ratings. The motor section of the UHDRS assesses motor features of Huntington's Disease (HD) with standardized ratings of oculo- motor function, dysarthria, chorea, dystonia, gait, and postural stability. Each of 15 assessments is rated on a scale of 0 (normal) to 4 (marked impairment) for a TMS range of 0-60. Negative change from baseline values indicate improvement. The change from baseline in TMS was analyzed using a Repeated Measures model (SAS® MIXED procedure with REPEATED sub-command). The model included the following fixed effects: categorical week in study by treatment interaction, country, neuroleptic use or no use, baseline TMS score, and categorical week in study by baseline TMS interaction. Baseline was the last observation prior to the first dose of study drug.

End point type

Primary

End point timeframe

Baseline (Day 0), Weeks 4, 8, 12, 16, 20, and 26 (or endpoint for the first treatment period)

End point values	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Number of subjects analysed	81 ^[1]	75 ^[2]	79 ^[3]	81 ^[4]	81 ^[5]
Units: units on a scale
least squares mean (standard error)	-4.79 ± 0.99	-3.37 ± 1.05	-3.09 ± 1.02	-4.13 ± 1.00	-2.74 ± 1.01

Notes
[1] - Full analysis set - those who received >= 1 dose of study drug and >=1 post-baseline efficacy.
[2] - FAS
[3] - FAS
[4] - FAS
[5] - FAS

TMS: Pridopidine 45 mg - Placebo

Statistical analysis description

The change from baseline in TMS was analyzed using a Repeated Measures model (SAS® MIXED procedure with REPEATED sub-command). The model included the following fixed effects: categorical week in study by treatment interaction, country, neuroleptic use or no use, baseline TMS score, and categorical week in study by baseline TMS interaction.

Comparison groups

Pridopidine 45 mg bid v Placebo

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3202

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

1.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

4.23

TMS: Pridopdine 67.5 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 67.5 mg bid v Placebo

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2266

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

4.46

TMS: Pridopdine 90 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 90 mg bid v Placebo

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6348

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

3.39

TMS: Pridopdine 112.5 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 112.5 mg bid v Placebo

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1447

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

4.8

Secondary: Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

Top of page

End point title

Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

End point description

mPPT includes 9 physical challenges, each scored on a 0-4 scale with 0 = unable to perform and 4 = performed well for a total score of 0-36. Positive change from baseline scores indicate improvement. The change from baseline in mPPT was analyzed using a Repeated Measures model (SAS® MIXED procedure with REPEATED sub-command). The model included the following fixed effects: categorical week in study by treatment interaction, country, neuroleptic use or no use, baseline mPPT score, and categorical week in study by baseline mPPT interaction.

End point type

Secondary

End point timeframe

Baseline (Day 0), Weeks 4, 8, 12, 16, 20, and 26 (or endpoint for the first treatment period)

End point values	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Number of subjects analysed	78 ^[6]	75 ^[7]	75 ^[8]	80 ^[9]	81 ^[10]
Units: units on a scale
least squares mean (standard error)	0.71 ± 0.41	0.75 ± 0.42	0.64 ± 0.41	0.70 ± 0.40	1.00 ± 0.40

Notes
[6] - FAS
[7] - FAS
[8] - FAS
[9] - FAS
[10] - FAS

mPPT: Pridopidine 45 mg - Placebo

Statistical analysis description

The change from baseline in mPPT was analyzed using a Repeated Measures model (SAS® MIXED procedure with REPEATED sub-command). The model included the following fixed effects: categorical week in study by treatment interaction, country, neuroleptic use or no use, baseline mPPT score, and categorical week in study by baseline mPPT interaction.

Comparison groups

Placebo v Pridopidine 45 mg bid

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9462

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

1.17

mPPT: Pridopidine 67.5 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 67.5 mg bid v Placebo

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8968

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.05

mPPT: Pridopidine 90 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 90 mg bid v Placebo

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9853

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

1.1

mPPT: Pridopidine 112.5 mg - Placebo

Statistical analysis description

Comparison groups

Pridopidine 112.5 mg bid v Placebo

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6063

Method

Mixed models analysis

Parameter type

LSM difference

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

1.4

Secondary: Participants with Adverse Events

Top of page

End point title

Participants with Adverse Events

End point description

An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

End point type

Secondary

End point timeframe

Day 1 to Week 52

End point values	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Number of subjects analysed	82 ^[11]	81 ^[12]	82 ^[13]	81 ^[14]	82 ^[15]
Units: participants
All AEs	62	63	69	71	67
AEs leading to discontinuation	6	10	16	12	15
Serious AEs	0	8	9	9	9
Severe AEs	5	7	10	12	11
AEs assessed as related to study drug	27	26	40	38	36

Notes
[11] - Safety
[12] - Safety
[13] - Safety
[14] - Safety
[15] - Safety

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Day 1 to Week 52

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Placebo

Reporting group description

Reporting group title

Pridopidine 45 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 90mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 90 mg which was taken from Day 28 to Week 52.

Reporting group title

Pridopidine 67.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 135 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 135 mg which was taken from Day 28 to Week 52.

Reporting group title

Pridopidine 90 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 180mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 180 mg which was taken from Day 28 to Week 52.

Reporting group title

Pridopidine 112.5 mg bid

Reporting group description

All patients in this study were administered 3 capsules twice daily (ie, 3 capsules in the morning and 3 capsules in the afternoon). Capsules either contained pridopidine in doses of 22.5 mg or 45 mg or placebo (sized to match the two active doses to assure the blind) and were supplied by the sponsor in medication packs to support the assigned total daily dose of 225 mg. Doses were titrated during the first 4 weeks, starting at a total daily dose of 45 mg, up to the assigned total daily dose of 225 mg which was taken from Day 28 to Week 52.

Serious adverse events	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 82 (0.00%)	8 / 81 (9.88%)	9 / 82 (10.98%)	9 / 81 (11.11%)	9 / 82 (10.98%)
number of deaths (all causes)	0	0	0	1	1
number of deaths resulting from adverse events
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myeloid leukaemia
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Laceration
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 82 (0.00%)	4 / 81 (4.94%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Head injury
subjects affected / exposed	0 / 82 (0.00%)	2 / 81 (2.47%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Face injury
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Grand mal convulsion
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Akathisia
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychomotor hyperactivity
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Optic ischaemic neuropathy
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Duodenal ulcer perforation
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine prolapse
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory failure
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	1 / 81 (1.23%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Psychiatric disorders
Mood disorder due to a general medical condition
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	1 / 81 (1.23%)	2 / 82 (2.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	1 / 81 (1.23%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urinary retention
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Peritonitis
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)	0 / 81 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 82 (0.00%)	0 / 81 (0.00%)	0 / 82 (0.00%)	0 / 81 (0.00%)	1 / 82 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Pridopidine 45 mg bid	Pridopidine 67.5 mg bid	Pridopidine 90 mg bid	Pridopidine 112.5 mg bid
Total subjects affected by non serious adverse events
subjects affected / exposed	45 / 82 (54.88%)	49 / 81 (60.49%)	63 / 82 (76.83%)	57 / 81 (70.37%)	53 / 82 (64.63%)
Investigations
Weight decreased
subjects affected / exposed	3 / 82 (3.66%)	4 / 81 (4.94%)	3 / 82 (3.66%)	3 / 81 (3.70%)	7 / 82 (8.54%)
occurrences all number	3	4	3	3	7
Creatinine renal clearance decreased
subjects affected / exposed	1 / 82 (1.22%)	5 / 81 (6.17%)	2 / 82 (2.44%)	3 / 81 (3.70%)	5 / 82 (6.10%)
occurrences all number	1	6	2	4	8
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	17 / 82 (20.73%)	16 / 81 (19.75%)	21 / 82 (25.61%)	13 / 81 (16.05%)	16 / 82 (19.51%)
occurrences all number	31	44	31	19	42
Contusion
subjects affected / exposed	3 / 82 (3.66%)	6 / 81 (7.41%)	6 / 82 (7.32%)	0 / 81 (0.00%)	3 / 82 (3.66%)
occurrences all number	3	7	8	0	4
Vascular disorders
Hypertension
subjects affected / exposed	1 / 82 (1.22%)	0 / 81 (0.00%)	1 / 82 (1.22%)	5 / 81 (6.17%)	2 / 82 (2.44%)
occurrences all number	1	0	1	6	2
Nervous system disorders
Headache
subjects affected / exposed	8 / 82 (9.76%)	7 / 81 (8.64%)	7 / 82 (8.54%)	11 / 81 (13.58%)	8 / 82 (9.76%)
occurrences all number	8	18	11	19	10
Chorea
subjects affected / exposed	1 / 82 (1.22%)	4 / 81 (4.94%)	13 / 82 (15.85%)	3 / 81 (3.70%)	7 / 82 (8.54%)
occurrences all number	1	4	15	3	8
Dizziness
subjects affected / exposed	2 / 82 (2.44%)	2 / 81 (2.47%)	6 / 82 (7.32%)	5 / 81 (6.17%)	6 / 82 (7.32%)
occurrences all number	2	2	12	5	8
Balance disorder
subjects affected / exposed	3 / 82 (3.66%)	2 / 81 (2.47%)	5 / 82 (6.10%)	1 / 81 (1.23%)	3 / 82 (3.66%)
occurrences all number	3	3	6	1	3
General disorders and administration site conditions
Fatigue
subjects affected / exposed	7 / 82 (8.54%)	3 / 81 (3.70%)	6 / 82 (7.32%)	7 / 81 (8.64%)	1 / 82 (1.22%)
occurrences all number	10	3	6	7	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	9 / 82 (10.98%)	9 / 81 (11.11%)	11 / 82 (13.41%)	11 / 81 (13.58%)	10 / 82 (12.20%)
occurrences all number	14	11	14	17	15
Vomiting
subjects affected / exposed	4 / 82 (4.88%)	5 / 81 (6.17%)	6 / 82 (7.32%)	5 / 81 (6.17%)	4 / 82 (4.88%)
occurrences all number	6	7	7	5	4
Nausea
subjects affected / exposed	4 / 82 (4.88%)	4 / 81 (4.94%)	7 / 82 (8.54%)	4 / 81 (4.94%)	3 / 82 (3.66%)
occurrences all number	4	6	10	6	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 82 (2.44%)	5 / 81 (6.17%)	2 / 82 (2.44%)	1 / 81 (1.23%)	5 / 82 (6.10%)
occurrences all number	2	5	2	1	5
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 82 (2.44%)	6 / 81 (7.41%)	6 / 82 (7.32%)	7 / 81 (8.64%)	5 / 82 (6.10%)
occurrences all number	2	6	6	8	5
Suicidal ideation
subjects affected / exposed	0 / 82 (0.00%)	2 / 81 (2.47%)	7 / 82 (8.54%)	1 / 81 (1.23%)	0 / 82 (0.00%)
occurrences all number	0	2	8	1	0
Insomnia
subjects affected / exposed	3 / 82 (3.66%)	5 / 81 (6.17%)	11 / 82 (13.41%)	9 / 81 (11.11%)	9 / 82 (10.98%)
occurrences all number	5	6	11	10	11
Irritability
subjects affected / exposed	7 / 82 (8.54%)	4 / 81 (4.94%)	6 / 82 (7.32%)	5 / 81 (6.17%)	2 / 82 (2.44%)
occurrences all number	8	4	7	5	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	3 / 82 (3.66%)	4 / 81 (4.94%)	3 / 82 (3.66%)	6 / 81 (7.41%)	5 / 82 (6.10%)
occurrences all number	3	4	3	9	6
Infections and infestations
Nasopharyngitis
subjects affected / exposed	7 / 82 (8.54%)	14 / 81 (17.28%)	12 / 82 (14.63%)	13 / 81 (16.05%)	15 / 82 (18.29%)
occurrences all number	8	21	16	15	23
Urinary tract infection
subjects affected / exposed	4 / 82 (4.88%)	3 / 81 (3.70%)	6 / 82 (7.32%)	4 / 81 (4.94%)	5 / 82 (6.10%)
occurrences all number	4	3	6	5	6

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

24 Sep 2013

Amendment 1 to the protocol (dated 24 September 2013) was issued before any patients were enrolled in the study. The following major procedural changes (not all-inclusive) were made to the protocol: - The duration of treatment with study drug was increased from 12 weeks to 26 weeks - The 45 mg dose was removed from the efficacy analyses - The timing of the DSMB meetings was changed - The opportunity to enter the open-label extension study was introduced - Rules for discontinuation of treatment groups were modified

03 Feb 2014

Amendment 2 to the protocol (dated 03 February 2014) was issued before any patients were enrolled in the study. Clarification that the mPPT will be used as the secondary efficacy endpoint - Increased frequency of DSMB meetings until 100 patients (20 from each treatment group) have completed two weeks of treatment on full dose - Clarification that Patients with a legal guardian should be consented according to local requirements - The EQ-5D-5L scale was added as an assessment - The possibility for patients to continue in the study after study drug discontinuation, due to safety or tolerability reasons, was introduced - Clarification regarding the number of capsules in the dispensed bottles - Change to time points at which exploratory efficacy endpoints (PBA-s, CIBIC-Plus, PDS, CGI-C, Walk-12, and TUG test) are assessed to reduce patient burden

16 Sep 2014

Amendment 3 to the protocol (dated 16 September 2014) was issued after 24 patients were enrolled into the study. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: - Extension of the period between screening and baseline visit to 12 weeks, to allow a switch in concomitant drugs if deemed medically justified and for the benefit of the patient by the investigator - Revised text to reflect that the investigator can unblind the treatment code in an emergency situation without prior approval of the sponsor - The ECG on Day 56 would be optional, unless required by local regulations - Clarification regarding the ECG at Week 2 (ie, that it will be performed in triplicate before the afternoon dose of that visit) - Prolonged QTcF deleted from baseline visit as an eligibility criterion. Prolonged QT at baseline will be handled according to the discontinuation rules specified in the protocol - Inclusion criterion was revised to read “IS equal to or less than 90% at the screening visit”, to include also patients with a IS of 90% - The protocol was updated to require that all serious adverse events be reported within 24 hours of when the investigator learns of the event, regardless of whether it’s a non-working day - Instructions on how to resume study drug after temporary interruption -Prohibited medications timing also changed from 6 weeks prior to screening to 6 weeks prior to baseline (eg, QT-interval prolonging meds, CYP2D6 metabolized meds, and tetrabenazine) - Rescreening of selected patients now permitted if not originally eligible for enrollment - Clarification regarding the time frame for suicide attempts prior to screening (ie, if the attempt or acts were performed within 1 year of screening) - New text regarding required reporting of suicidality as an adverse event

12 Jan 2015

Amendment 4 to the protocol (dated 12 January 2015) was issued after 133 patients were enrolled into the study. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: - endpoints modified and/or added to reflect the study extension - days of assessments and procedures modified to reflect changes in time points - clarification to allow only 1 titration during the entire study period - new text added to define the population sets that will be used to analyze the data from the second study period

31 Mar 2016

Amendment 5 to the protocol (dated 31 March 2016) was issued after 408 patients were enrolled into the study. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study. - Addition of 2 telephone calls for safety evaluation (at Weeks 40 to 44 and Weeks 46 to 51) including C-SSRS and an abbreviated PBA-s assessment - Addition of suicidal ideations and suicide attempts as protocol-defined adverse events for expedited reporting - Addition of discontinuation criteria for individual patients and stopping rules for treatment groups - Clarification of study conduct - Revision of the Study Procedures and Assessments and Overall Study Schema to reflect the amended study design

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg Twice-Daily versus Placebo for Symptomatic Treatment in Patients with Huntington’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Total Motor Score (TMS) at Week 26

Primary: Change from Baseline in Total Motor Score (TMS) at Week 26

Secondary: Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

Secondary: Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

Secondary: Participants with Adverse Events

Secondary: Participants with Adverse Events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg Twice-Daily versus Placebo for Symptomatic Treatment in Patients with Huntington’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Total Motor Score (TMS) at Week 26

Primary: Change from Baseline in Total Motor Score (TMS) at Week 26

Secondary: Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

Secondary: Change from Baseline in Modified Physical Performance Test (mPPT) at Week 26

Secondary: Participants with Adverse Events

Secondary: Participants with Adverse Events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg Twice-Daily versus Placebo for Symptomatic Treatment in Patients with Huntington’s Disease