Effect of Fenofibrate on Sleep Apnea Syndrome

• Sponsor: Solvay Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00816829
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Objectives: to investigate for the potential effect of fenofibrate on symptoms and biological changes associated with sleep apnea syndrome.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia; Sleep Apnea Syndrome; Overweight; Obesity	Drug: Placebo; Drug: Fenofibrate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 1-month, Randomized, Double-blind, Placebo-controlled Study of Fenofibrate 145 mg Tablet in Patients With Sleep Apnea Syndrome
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Fenofibrate-matching placebo tablet	Drug: Placebo; Fenofibrate-matching placebo tablet
Experimental: 2 145 mg NanoCrystal fenofibrate tablet	Drug: Fenofibrate; 145 mg NanoCrystal tablet

Outcome Measures

Primary Outcome Measures

1. Obstructive Apneas [at one month of treatment]

   Total number of obstructive apneas during sleep during one night after one month of treatment (i.e. an occlusion of the airways accompanied by ineffective respiratory efforts).

2. Desaturations [at one month of treatment]

   Total number of desaturation events (i.e. defined as a decrease by 3 - 4% in oxygen saturation) during sleep during one night after one month of treatment.

3. Sleep Time With Oxygen Saturation Below 90% [at one month of treatment]

   Percentage of Sleep time with oxygen saturation below 90% (measured by oximetry). Marker of consequences of apneas/hypopneas on arterial oxygenation during sleep during one night after one month of treatment. Higher percentage are worst for the patients.

4. Apneas [at one month of treatment]

   Total number of episodes of apneas (i.e. cessation of breathing for at least 10 seconds) from central, obstructive or mixed origin during sleep during one night after one month of treatment

5. Hypopneas [at one month of treatment]

   Total number of episodes of hypopneas (i.e. 50% to 80% reduction in airflow with a decrease of 3-4% in arterial oxygen saturation) during sleep during one night after one month of treatment.

6. Index Apnea/Hypopnea [at one month of treatment]

   Average number of apneas and/or hypopneas per hour of sleep during one night after one month of treatment.

7. Mixed Apneas [at one month of treatment]

   Total number of mixed apneas (i.e. sleep apneas that have both obstructive and central component) during sleep during one night after one month of treatment.

8. Central Apneas [at one month of treatment]

   Total number of central apneas (i.e. apneas with no respiratory effort present) during sleep during one night after one month of treatment.

9. Index of Apneas [at one month of treatment]

   Average number of apneas per hour of sleep during one night after one month of treatment.

10. Index of Hypopneas [at one month of treatment]

    Average number of hypopneas per hour of sleep during one night after one month of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Having previous diagnosis of sleep apnea not treated with Continuous Positive Airway Pressure (CPAP) or presenting clinical symptoms of sleep apnea

• Overweight or obese, with BMI >= 25 kg/m² and < 40 kg/m².

• Known moderate hypertriglyceridemia, with fasting Triglycerides level >= 2.0 and < 6.0 mmol/L within 3 months before the inclusion.

Exclusion Criteria:

• indication for immediate CPAP

• other known endocrine disease, except treated and adequately controlled hypothyroidism

• renal failure or plasma creatinine level >130 µmol/L

• current chronic liver disease or ALanine Amino Transferase (ALT)> 2 times the upper normal limit (UNL)

• symptomatic gallbladder disease

• known muscular disease or creatine phosphokinase (CK) > 3 times UNL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 1	Paris		France

Sponsors and Collaborators

• Solvay Pharmaceuticals

Investigators

• Study Director: Global Clinical Director Solvay, Solvay Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00816829
• Other Study ID Numbers: C LF178P 05 01; 2005-000548-98
• First Posted: Jan 5, 2009
• Last Update Posted: Jul 22, 2009
• Last Verified: Jul 1, 2009

• Keywords provided by , ,: Dyslipidemia; Sleep Apnea Syndromes; Fenofibrate; Obese; Overweight or obese patients
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Dyslipidemias; Syndrome; Overweight; Fenofibrate

Study Results

Participant Flow

Recruitment Details	Subjects were recruited and treated in a hospital in Paris between September 2005 and January 2008
Pre-assignment Detail	In total 34 subjects were randomly allocated to treatment (i.e. Subjects Started). All the subjects received the study drug and completed the study. The study was prematurely terminated because of low recruitment.

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Period Title: Overall Study
STARTED	16	18
COMPLETED	16	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Fenofibrate	Total
Arm/Group Description	Placebo	Fenofibrate 145 mg	Total of all reporting groups
Overall Participants	16	18	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (6.5)	55.9 (5.4)	55.6 (5.8)
Sex: Female, Male (Count of Participants)
Female	6 37.5%	6 33.3%	12 35.3%
Male	10 62.5%	12 66.7%	22 64.7%
Region of Enrollment (participants) [Number]
France	16 100%	18 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Obstructive Apneas
Description	Total number of obstructive apneas during sleep during one night after one month of treatment (i.e. an occlusion of the airways accompanied by ineffective respiratory efforts).
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed using the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of obstructive apneas]	30.5	15.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Desaturations
Description	Total number of desaturation events (i.e. defined as a decrease by 3 - 4% in oxygen saturation) during sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 in fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of desaturations]	171.0	130.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.203
	Comments
	Method	ANCOVA
	Comments

3. Primary Outcome

Title	Sleep Time With Oxygen Saturation Below 90%
Description	Percentage of Sleep time with oxygen saturation below 90% (measured by oximetry). Marker of consequences of apneas/hypopneas on arterial oxygenation during sleep during one night after one month of treatment. Higher percentage are worst for the patients.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Percentage of sleep time]	11.5	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using Wilcoxon Test on data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Apneas
Description	Total number of episodes of apneas (i.e. cessation of breathing for at least 10 seconds) from central, obstructive or mixed origin during sleep during one night after one month of treatment
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of apneas]	31.0	20.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.199
	Comments
	Method	ANCOVA
	Comments

5. Primary Outcome

Title	Hypopneas
Description	Total number of episodes of hypopneas (i.e. 50% to 80% reduction in airflow with a decrease of 3-4% in arterial oxygen saturation) during sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of hypopneas]	69.5	63.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.114
	Comments
	Method	ANCOVA
	Comments

6. Primary Outcome

Title	Index Apnea/Hypopnea
Description	Average number of apneas and/or hypopneas per hour of sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number per hour of sleep]	22.5	17.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.533
	Comments
	Method	ANCOVA
	Comments

7. Primary Outcome

Title	Mixed Apneas
Description	Total number of mixed apneas (i.e. sleep apneas that have both obstructive and central component) during sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of mixed apneas]	0.0	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.521
	Comments
	Method	ANCOVA
	Comments

8. Primary Outcome

Title	Central Apneas
Description	Total number of central apneas (i.e. apneas with no respiratory effort present) during sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number of central apneas]	0.0	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	ANCOVA
	Comments

9. Primary Outcome

Title	Index of Apneas
Description	Average number of apneas per hour of sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number per hour of sleep]	4.0	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.264
	Comments
	Method	ANCOVA
	Comments

10. Primary Outcome

Title	Index of Hypopneas
Description	Average number of hypopneas per hour of sleep during one night after one month of treatment.
Time Frame	at one month of treatment

Outcome Measure Data

Analysis Population Description

The analysis was performed on the total sample of randomized subjects (16 on placebo and 18 on fenofibrate).

Arm/Group Title	Placebo	Fenofibrate
Arm/Group Description	Placebo	Fenofibrate 145 mg
Measure Participants	16	18
Median (Full Range) [Number per hour of sleep]	11.0	9.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fenofibrate
	Comments	Comparison between groups was performed using an ANCOVA on log-transformed data at one month after the start of the treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Placebo		Fenofibrate
Arm/Group Description	Placebo		Fenofibrate 145 mg
All Cause Mortality
	Placebo		Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/ (NaN)		1/ (NaN)
Surgical and medical procedures
Metabolic and medical procedures	0/16 (0%)		1/18 (5.6%)
Other (Not Including Serious) Adverse Events
	Placebo		Fenofibrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		3/ (NaN)
Gastrointestinal disorders
Abdominal distension	0/16 (0%)		1/18 (5.6%)
Infections and infestations
Cystitis	0/16 (0%)		1/18 (5.6%)
Metabolism and nutrition disorders
Diabetes mellitus non-insulin-dependent	0/16 (0%)		1/18 (5.6%)
Musculoskeletal and connective tissue disorders
Back Pain	1/16 (6.3%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic	0/16 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Rash	0/16 (0%)		1/18 (5.6%)

Limitations/Caveats

Only treatment emergent events have been presented. They are defined as events started at or after the 1st administration of study medication and includes events started prior to the 1st administration but which worsened after the 1st intake.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review.