Trial Outcomes & Findings for Clarithromycin for the Treatment of Hypersomnia (NCT NCT01146600)

NCT ID: NCT01146600

Last Updated: 2017-11-06

Results Overview

Median reaction time on the PVT at the end of the second week of treatment. Lower values reflect faster reaction times (I.e., greater vigilance). Note that the PVT provides a median of reaction times to all stimuli (\~100) presented during the 10 minute PVT test. Each subject had two PVT tests at each visit, resulting in two median values. These were averaged, and then, for the purposes of this outcome, we then obtained the MEAN across multiple subjects for each condition (baseline, clarithromycin week 2, placebo week 2)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 26 participants
• Primary outcome timeframe: week 2 of each intervention
• Results posted on: 2017-11-06

Participant Flow

Most subjects were recruited from the patient population of a single Sleep Center affiliated with Emory University School of Medicine. One subject contacted investigators for participation after reading of the study on clinicaltrials.gov. The first patient was recruited 3/5/11 and the final patient completed the study on 9/28/12.

All subjects underwent screening laboratories after enrollment but before beginning medication. In the case of abnormal laboratory results (n = 2), subjects did not begin treatment with either study drug (clarithromycin or placebo). One patient dropped out after consent but before randomization (because of scheduling conflict).

Participant milestones

Measure	Clarithromycin, Then Placebo Subjects randomized to receive clarithromycin first (for two weeks), then matched placebo (for an additional two weeks, following the washout)	Placebo, Then Clarithromycin Subjects randomized to receive placebo first (for two weeks), then clarithromycin (for an additional two weeks, following the washout)
Period 1 (Weeks 1 & 2) STARTED	13	10
Period 1 (Weeks 1 & 2) COMPLETED	10	10
Period 1 (Weeks 1 & 2) NOT COMPLETED	3	0
Washout (Week 3) STARTED	10	10
Washout (Week 3) COMPLETED	10	10
Washout (Week 3) NOT COMPLETED	0	0
Period 2 (Weeks 4 & 5) STARTED	10	10
Period 2 (Weeks 4 & 5) COMPLETED	10	10
Period 2 (Weeks 4 & 5) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clarithromycin for the Treatment of Hypersomnia

Baseline characteristics by cohort

Measure	Clarithromycin, Then Placebo n=13 Participants Subjects will be randomized to group A or group B. The order of presentation of placebo and clarithromycin will be opposite in these two groups, but investigators and subjects will remain blinded to group allocation and order of treatment presentation within the groups. Clarithromycin followed by placebo : Clarithromycin 500 mg po bid (with breakfast and lunch) for two weeks, then one week with no medication, then matched placebo po bid (with breakfast and lunch) for two weeks.	Placebo, Then Clarithromycin n=10 Participants Subjects will be randomized to group A or group B. The order of presentation of placebo and clarithromycin will be opposite in these two groups, but investigators and subjects will remain blinded to group allocation and order of treatment presentation within the groups. Placebo then Clarithromycin : Matched placebo po bid (with breakfast and lunch) for two weeks, then one week with no intervention, then clarithromycin 500 mg po bid (with breakfast and lunch) for two weeks	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	33.8 years STANDARD_DEVIATION 13.4 • n=5 Participants	34.7 years STANDARD_DEVIATION 14.5 • n=7 Participants	34.2 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	10 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: week 2 of each intervention

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

Median reaction time on the PVT at the end of the second week of treatment. Lower values reflect faster reaction times (I.e., greater vigilance).

Note that the PVT provides a median of reaction times to all stimuli (~100) presented during the 10 minute PVT test. Each subject had two PVT tests at each visit, resulting in two median values. These were averaged, and then, for the purposes of this outcome, we then obtained the MEAN across multiple subjects for each condition (baseline, clarithromycin week 2, placebo week 2)

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
Psychomotor Vigilance Task (PVT) Reaction Time	279.1 Msec Standard Deviation 77.3	311.6 Msec Standard Deviation 114.1	333.8 Msec Standard Deviation 291.4

SECONDARY outcome

Timeframe: week 1

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

median reaction time on the PVT at week 1 of each intervention. Lower values reflect faster reaction times (i.e., better vigilance)

Note that the PVT provides a median of reaction times to all stimuli (~100) presented during the 10 minute PVT test. Each subject had two PVT tests at each visit, resulting in two median values. These were averaged, and then, for the purposes of this outcome, we then obtained the MEAN across multiple subjects for each condition (baseline, clarithromycin week 1, placebo week 1)

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
PVT Median Reaction Time at Week 1	285.4 Msec Standard Deviation 71.3	308.4 Msec Standard Deviation 120.6	333.8 Msec Standard Deviation 291.4

SECONDARY outcome

Timeframe: baseline, then after 1 week and 2 weeks on each study drug

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

Number of lapses (no response for > 500 msec) on the PVT, averaged by subject across all administrations for a given drug condition (i.e. administered twice at baseline, four times on clarithromycin (twice during week 1 and twice during week 2), and four times on placebo (twice during week 1 and twice during week 2)). Higher numbers indicate worse vigilance.

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
PVT Number of Lapses	5.7 Number of lapses Standard Deviation 11.3	10.3 Number of lapses Standard Deviation 18.7	6.5 Number of lapses Standard Deviation 16.9

SECONDARY outcome

Timeframe: baseline, then after 1 week and 2 weeks on each study drug

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

Scores on the Epworth Sleepiness Scale (ESS) were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)).

ESS scores can range from 0 to 24. Higher scores indicate higher levels of sleepiness.

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
Epworth Sleepiness Scale	10.1 units on a scale Standard Deviation 5.4	14.1 units on a scale Standard Deviation 3.7	15.0 units on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: baseline, then after 1 week and 2 weeks on each study drug

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

Scores on the Functional Outcomes of Sleep Questionnaire (FOSQ) were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)).

Scores on the FOSQ can range from 5 to 20. Higher FOSQ scores indicate less impairment due to sleepiness.

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
FOSQ	16.6 units on a scale Standard Deviation 2.4	14.4 units on a scale Standard Deviation 2.7	13.9 units on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: baseline, then after 1 week and 2 weeks on each study drug

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

The SF-36 is a health outcome scale with multiple subsections. Subjects were administered the entire SF-36; this analysis is of the vitality subscore provided by this scale. Scores were averaged by subject across all administrations for a given drug condition (i.e. administered once at baseline, twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)).

The vitality subscore is calculated using four questions from the SF-36, and can range from 0 to 100. Higher scores reflect more vitality.

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
SF-36, Vitality Subscale	48.9 units on a scale Standard Deviation 26.9	28.0 units on a scale Standard Deviation 22.5	25.0 units on a scale Standard Deviation 21.6

SECONDARY outcome

Timeframe: baseline, then after 1 week and 2 weeks on each study drug

Population: Analysis was performed on all subjects who took both study drugs (i.e., clarithromycin and placebo)

Scores on the Pittsburgh Sleep Quality Index (PSQI), a questionnaire based assessment of sleep quality. Scores were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)).

Scores on the PSQI can range from 0 to 21. Higher scores indicate poorer sleep quality.

Outcome measures

Measure	Clarithromycin n=20 Participants Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 Participants Matched placebo with breakfast and with lunch for two weeks	Baseline n=20 Participants Baseline values (prior to first study drug) for the 20 subjects who completed both treatment arms.
PSQI	5.8 units on a scale Standard Deviation 3.9	6.3 units on a scale Standard Deviation 2.8	6.7 units on a scale Standard Deviation 3.5

Adverse Events

Clarithromycin

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Clarithromycin n=22 participants at risk Clarithromycin 500 mg with breakfast and 500 mg with lunch for two weeks	Placebo n=20 participants at risk Matched placebo with breakfast and with lunch for two weeks
Gastrointestinal disorders abdominal pain	13.6% 3/22	5.0% 1/20
Psychiatric disorders anxiety	4.5% 1/22	5.0% 1/20
General disorders bad taste or smell	68.2% 15/22	0.00% 0/20
Gastrointestinal disorders bloating/gas	9.1% 2/22	5.0% 1/20
Musculoskeletal and connective tissue disorders chest discomfort	0.00% 0/22	5.0% 1/20
Gastrointestinal disorders diarrhea	18.2% 4/22	25.0% 5/20
Nervous system disorders dizziness	4.5% 1/22	5.0% 1/20
Nervous system disorders feeling "jittery" or "hyper"	13.6% 3/22	5.0% 1/20
Nervous system disorders headache	13.6% 3/22	25.0% 5/20
General disorders hiccups	0.00% 0/22	5.0% 1/20
Gastrointestinal disorders change in appetite (increase or decrease)	9.1% 2/22	5.0% 1/20
General disorders sweating, flushing, or feeling hot	9.1% 2/22	5.0% 1/20
Nervous system disorders insomnia	27.3% 6/22	15.0% 3/20
Musculoskeletal and connective tissue disorders knee pain	0.00% 0/22	5.0% 1/20
Gastrointestinal disorders nausea	31.8% 7/22	15.0% 3/20
General disorders nose bleed	9.1% 2/22	0.00% 0/20
Infections and infestations symptoms of upper respiratory infection	0.00% 0/22	15.0% 3/20
Cardiac disorders syncope	0.00% 0/22	5.0% 1/20
Nervous system disorders tremor	4.5% 1/22	5.0% 1/20
Gastrointestinal disorders unspecified gastrointestinal distress	22.7% 5/22	25.0% 5/20

Additional Information

Lynn Marie Trotti, MD, MSc

Emory University School of Medicine

Phone: 404-728-4752

Email: lbecke2@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place