IONIA: Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia

• Sponsor: Santhera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00537680
• Collaborator: (none)
• Enrollment: 70
• Locations: 2
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 35
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

This study is meant to assess the effectiveness of idebenone on neurological outcome measures in patients with Friedreich's Ataxia over a 6 months period.

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

Detailed Description

The study involves 6 clinic visits and upon completion the possibility to join a 12 months extension study where all patients will receive high dose Idebenone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 mid dose Idebenone	Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day
Experimental: 2 high dose Idebenone	Drug: Idebenone; Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day
Placebo Comparator: 3	Drug: Placebo; Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.

Outcome Measures

Primary Outcome Measures

1. ICARS [baseline and 6 months]

   International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Scores for each subscale quantify the extent of ataxia in each clinically important area. Subscale scores are summed to give a total score ranging from 0 (best) to 100 (worst).

Secondary Outcome Measures

1. FARS [6 Months]

   Friedreich's Ataxia Rating Scale

2. ADL of FARS [6 Months]

   ADL=Activities of Daily Living

3. FACT [6 Months]

   Friedreich's Ataxia Composite Test

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Documented diagnosis of Friedreich's Ataxia (FRDA) with confirmed FRDA mutations

• Patients 8 - 17 years of age at baseline

• Patients with a body weight greater than 25 kg/55 lbs at baseline

• Patients able to walk at least 10 meters without accompanying person (ICARS Walking Capacities score ≤6) at screening and baseline

• Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication

• Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)

Exclusion criteria:

• Treatment with idebenone, Coenzyme Q10 or vitamin E (if taken at a dose 5 times above the daily requirement) within the past month

• Patients with International Cooperative Ataxia Rating Scale (ICARS) score of greater than 54 or less than 10 at screening

• Pregnancy and/or breast-feeding

• Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of Aspartate Aminotransferase (AST; also known as GOT), Alanine Aminotransferase (ALT; also known as GPT) or creatinine

• History of abuse of drugs or alcohol

• Participation in the previous (Phase II) study of idebenone at the National Institutes of Health (NIH)

• Participation in a trial of another investigational drug within the last 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine, UCLA	Los Angeles	California	United States	90095-1769
2	The Children's Hopsital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Santhera Pharmaceuticals

Investigators

• Principal Investigator: Susan Perlman, MD, University of California, Los Angeles
• Principal Investigator: David Lynch, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Santhera Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00537680
• Other Study ID Numbers: SNT-III-002
• First Posted: Oct 1, 2007
• Last Update Posted: Feb 3, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Santhera Pharmaceuticals: Friedreich's Ataxia; Idebenone; ICARS
• Additional relevant MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Ubiquinone; Idebenone

Study Results

Participant Flow

Arm/Group Title	Mid Dose Idebenone	High Dose Idebenone	Placebo
Arm/Group Description	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 450 mg/day (1 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 900 mg/day (2 x 150 mg tablet, t.i.d.)	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 1350 mg/day (2 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 2250 mg/day (2 x 150 mg tablet, t.i.d.)	Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Period Title: Overall Study
STARTED	22	24	24
COMPLETED	22	22	24
NOT COMPLETED	0	2	0

Baseline Characteristics

Arm/Group Title	Mid Dose Idebenone	High Dose Idebenone	Placebo	Total
Arm/Group Description	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 450 mg/day (1 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 900 mg/day (2 x 150 mg tablet, t.i.d.)	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 1350 mg/day (2 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 2250 mg/day (2 x 150 mg tablet, t.i.d.)	Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.	Total of all reporting groups
Overall Participants	22	24	24	70
Age (Count of Participants)
<=18 years	22 100%	24 100%	24 100%	70 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.93 (2.54)	13.44 (3.03)	13.69 (2.77)	13.68 (2.76)
Sex: Female, Male (Count of Participants)
Female	7 31.8%	14 58.3%	16 66.7%	37 52.9%
Male	15 68.2%	10 41.7%	8 33.3%	33 47.1%
Region of Enrollment (participants) [Number]
United States	22 100%	24 100%	24 100%	70 100%

Outcome Measures

1. Primary Outcome

Title	ICARS
Description	International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Scores for each subscale quantify the extent of ataxia in each clinically important area. Subscale scores are summed to give a total score ranging from 0 (best) to 100 (worst).
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mid Dose Idebenone	High Dose Idebenone	Placebo
Arm/Group Description	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 450 mg/day (1 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 900 mg/day (2 x 150 mg tablet, t.i.d.)	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 1350 mg/day (2 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 2250 mg/day (2 x 150 mg tablet, t.i.d.)	Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
Measure Participants	22	24	24
Mean (Standard Deviation) [ICARS points]	-2.5 (6.3)	-2.4 (4.8)	-1.3 (4.4)

2. Secondary Outcome

Title	FARS
Description	Friedreich's Ataxia Rating Scale
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	ADL of FARS
Description	ADL=Activities of Daily Living
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	FACT
Description	Friedreich's Ataxia Composite Test
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	"0" means none.
Arm/Group Title	Mid Dose Idebenone		High Dose Idebenone		Placebo
Arm/Group Description	25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 450 mg/day (1 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 900 mg/day (2 x 150 mg tablet, t.i.d.)		25 kg/55 lbs to ≤45 kg/99 lbs: idebenone 1350 mg/day (2 x 150 mg tablet, t.i.d.) >45 kg/99 lbs: idebenone 2250 mg/day (2 x 150 mg tablet, t.i.d.)		Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.
All Cause Mortality
	Mid Dose Idebenone		High Dose Idebenone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mid Dose Idebenone		High Dose Idebenone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		2/24 (8.3%)		0/24 (0%)
Blood and lymphatic system disorders
idiopathic thrombocytopenic purpura	0/22 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0
General disorders
chest pain	0/22 (0%)	0	1/24 (4.2%)	2	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Mid Dose Idebenone		High Dose Idebenone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/22 (81.8%)		23/24 (95.8%)		21/24 (87.5%)
Gastrointestinal disorders
Gastrointestinal disorders	8/22 (36.4%)		15/24 (62.5%)		12/24 (50%)
General disorders
General disorders	10/22 (45.5%)		9/24 (37.5%)		9/24 (37.5%)
Infections and infestations
Infections	11/22 (50%)		15/24 (62.5%)		16/24 (66.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal & connective tissue disorders	7/22 (31.8%)		10/24 (41.7%)		7/24 (29.2%)
Nervous system disorders
Nervous system disorders	10/22 (45.5%)		14/24 (58.3%)		12/24 (50%)

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.