Patient Reported Outcomes in Friedreich's Ataxia Patients After Withdrawal From Treatment With Idebenone (PROTI)

• Sponsor: Santhera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01303406
• Collaborator: (none)
• Enrollment: 29
• Locations: 6
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase IIIb Double-Blind, Randomised, Placebo-Controlled Study. The aim is to further investigate the effects of idebenone in patients with Friedreich's ataxia.

The objective of the PROTI study is to establish whether patients can correctly determine which treatment assignment (placebo or idebenone) they received during the randomised phase of the trial, and identify any potential changes on symptoms or activities.

Condition or Disease	Intervention/Treatment	Phase
Friedreich's Ataxia	Drug: Idebenone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIIb Double-Blind, Randomised, Placebo-Controlled Study of Patient Reported Outcomes in Friedreich's Ataxia Patients After Withdrawal From Treatment With Idebenone
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals	Drug: Placebo
Experimental: idebenone Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals	Drug: Idebenone; All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).; Other Names: Catena (approved name in Canada)

Outcome Measures

Primary Outcome Measures

1. Patient Assessment of Treatment Assignment: Comparison of the Proportions of Patients Randomised to Idebenone and Placebo Who Assessed That They Received Idebenone [At 2 months after study start]

   The primary efficacy endpoint was the comparison of the number of patients randomized to idebenone and placebo, who assessed that they received idebenone treatment.

Secondary Outcome Measures

1. Comparison of the Percentage of Participants Randomised to Idebenone and Placebo Who Withdrew Early Due to Recurrence or Worsening of FRDA Symptoms [Within 2 months (i.e. Early withdrawal visit)]

   There was no Withdrawal due to recurrence or worsening of FRDA symptoms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of V5 (Month 12), V6 (Month 18), or V7 (Month 24) in the MICONOS extension study

• Patients who in the opinion of the investigator are able to comply with the requirements of the study

• Body weight ≥ 25kg

• Negative urine pregnancy test

Exclusion Criteria:

• AE during the course of the MICONOS extension study which in the opinion of the investigator is attributable to idebenone and precludes further treatment with idebenone

• Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal SGOT, SGPT or creatinine

• Parallel participation in another clinical drug trial

• Pregnancy or breast-feeding

• Abuse of drugs or alcohol

• Any change of concomitant medication within the last 30 days that in the opinion of the investigator the intake could negatively impact the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Innsbruck		Austria
2		Bonn		Germany
3		München		Germany
4		Tübingen		Germany
5		Groningen		Netherlands
6	The National Hospital, University College London	London		United Kingdom	WC 1N 3BG

Sponsors and Collaborators

• Santhera Pharmaceuticals

Investigators

• Principal Investigator: Paola Giunti, M.D, Institute of Neurology, The National Hospital, University College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Santhera Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01303406
• Other Study ID Numbers: SNT-III-004
• First Posted: Feb 24, 2011
• Last Update Posted: Mar 9, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Santhera Pharmaceuticals: randomized withdrawal; idebenone; friedreich's ataxia; Miconos; Patient reported outcome; ICARS
• Additional relevant MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Idebenone

Study Results

Participant Flow

Arm/Group Title	Placebo	Idebenone
Arm/Group Description	Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).	Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).
Period Title: Overall Study
STARTED	13	16
COMPLETED	13	15
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Placebo	Idebenone	Total
Arm/Group Description	Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).	Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).	Total of all reporting groups
Overall Participants	13	16	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.7 (16.5)	35.8 (16.9)	37.1 (16.5)
Sex: Female, Male (Count of Participants)
Female	4 30.8%	7 43.8%	11 37.9%
Male	9 69.2%	9 56.3%	18 62.1%
Region of Enrollment (participants) [Number]
Germany	3 23.1%	5 31.3%	8 27.6%
United Kingdom	7 53.8%	7 43.8%	14 48.3%
Austria	2 15.4%	2 12.5%	4 13.8%
Netherlands	1 7.7%	2 12.5%	3 10.3%

Outcome Measures

1. Primary Outcome

Title	Patient Assessment of Treatment Assignment: Comparison of the Proportions of Patients Randomised to Idebenone and Placebo Who Assessed That They Received Idebenone
Description	The primary efficacy endpoint was the comparison of the number of patients randomized to idebenone and placebo, who assessed that they received idebenone treatment.
Time Frame	At 2 months after study start

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Idebenone
Arm/Group Description	Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).	Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).
Measure Participants	13	16
Number [participants]	6 46.2%	8 50%

2. Secondary Outcome

Title	Comparison of the Percentage of Participants Randomised to Idebenone and Placebo Who Withdrew Early Due to Recurrence or Worsening of FRDA Symptoms
Description	There was no Withdrawal due to recurrence or worsening of FRDA symptoms
Time Frame	Within 2 months (i.e. Early withdrawal visit)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Idebenone
Arm/Group Description	Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).	Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).
Measure Participants	13	16
Number [percentage of patients]	0	0

Adverse Events

Arm/Group Title	Placebo		Idebenone
Arm/Group Description	Following the body weight, patients will be allocated to one of the following regimen: Placebo Patients < 45 kg - 3 tablets 3 times a day with meals Placebo Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).		Following the body weight, patients will be allocated to one of the following regimen: Idebenone Patients < 45 kg - 3 tablets 3 times a day with meals Idebenone Patients > 45 kg - 5 tablets 3 times a day with meals Idebenone: All PROTI patients randomised to idebenone treatment will receive high dose idebenone. This is defined according to body weight. In patients weighing 45 kg or less, it is 1350 mg/day (3 x 150 mg tablets three times per day with meals). In patients weighing more than 45 kg, it is 2250 mg/day (5 x 150 mg tablets three times per day with meals).
All Cause Mortality
	Placebo		Idebenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Idebenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Fractured femur	0/13 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Dislocated hip	0/13 (0%)		1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Placebo		Idebenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		12/16 (75%)
Cardiac disorders
Atrial fibrillation	0/13 (0%)		1/16 (6.3%)
Endocrine disorders
Parathyroid gland enlargement	0/13 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Diarrhea	0/13 (0%)		2/16 (12.5%)
Gastrointestinal disorder	0/13 (0%)		1/16 (6.3%)
General disorders
Fatigue	0/13 (0%)		3/16 (18.8%)
Pain	1/13 (7.7%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Fall	3/13 (23.1%)		3/16 (18.8%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/13 (7.7%)		1/16 (6.3%)
Nervous system disorders
Speech disorder	2/13 (15.4%)		2/16 (12.5%)
Headache	1/13 (7.7%)		1/16 (6.3%)
Tremor	1/13 (7.7%)		0/16 (0%)
Psychiatric disorders
Insomnia	1/13 (7.7%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.