A Proof of Concept Study to Evaluate the Effects of Tasimelteon and Placebo in Travelers With Jet Lag Disorder

• Sponsor: Vanda Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03291041
• Collaborator: (none)
• Enrollment: 25
• Locations: 3
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

A Proof of Concept Study to Evaluate the Effects of Tasimelteon and Placebo in Travelers With Jet Lag Disorder

Condition or Disease	Intervention/Treatment	Phase
Jet Lag Disorder	Drug: Tasimelteon; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Proof of Concept Study to Evaluate the Effects of Tasimelteon and Placebo in Travelers With Jet Lag Disorder
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tasimelteon tasimelteon, administered as oral capsule(s)	Drug: Tasimelteon; capsule
Placebo Comparator: Placebo Placebo, administered as oral capsule(s)	Drug: Placebo; capsule

Outcome Measures

Primary Outcome Measures

1. Total Sleep Time in the First Two-Thirds of the Night on the Night(s) Most Likely to be Disrupted [4 days]

   Measured using polysomnography (PSG) and analyzed as change from baseline. Examination of the observational phase baseline data demonstrated that Night 3 was the night most disrupted.

Secondary Outcome Measures

1. Patient Global Impression of Severity (PGI-S) Day 4 [1 Day]

   Self-reported global index measure analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight. The PGI-S is a single question asking the subject to rate their jet-lag condition at the present time on a scale of 1 "Normal" to 4 "Severe".

2. Total Sleep Time in the First Two-Thirds of the Night (All 3 Nights) [3 Days]

   Measured using polysomnography (PSG) and analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight.

3. Subjective Total Sleep Time on Night 3 [1 Day]

   Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline

4. Subjective Sleep Quality Night 3 [1 Day]

   Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline. Sleep quality was ranked from 1 "Poor" to 5 "Excellent" and was the subscale of the post-sleep questionnaire used to determine subjective sleep quality.

5. Subjective Sleep Latency Night 3 [1 Day]

   Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline

6. Subjective Wake After Sleep Onset Night 3 [1 Day]

   Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline

7. Karolinska Sleepiness Scale Day 4 [1 Day]

   Self-reported fatigue measure analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight. The KSS is a single question asking the subject to rate how sleepy they feel at that moment on a 9-point scale where 1 = extremely awake and 9 = extremely sleepy/fighting to stay wake.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ability and acceptance to provide written consent

• Men or women between 18-75 years

• Body Mass Index of ≥ 18 and ≤ 30 kg/m2

Exclusion Criteria:

• History (within the 12 months prior to screening) of psychiatric disorders

• Major surgery, trauma, illness or immobile for 3 or more days within the past month

• Pregnancy or recent pregnancy (within 6 weeks)

• A positive test for drugs of abuse at the screening visit

• Any other sound medical reason as determined by the clinical investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanda Investigational Site	Alameda	California	United States	94501
2	Vanda Investigational Site	Santa Monica	California	United States	90404
3	Vanda Investigational Site	Chevy Chase	Maryland	United States	20815

Sponsors and Collaborators

• Vanda Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 18, 2018

More Information

Publications

None provided.

• Responsible Party: Vanda Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03291041
• Other Study ID Numbers: VP-VEC-162-2102
• First Posted: Sep 25, 2017
• Last Update Posted: Nov 3, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Jet Lag Syndrome

Study Results

Participant Flow

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Period Title: Overall Study
STARTED	13	12
COMPLETED	13	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Tasimelteon	Placebo	Total
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule	Total of all reporting groups
Overall Participants	13	12	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (13.47)	48.2 (16.06)	49.8 (14.54)
Sex: Female, Male (Count of Participants)
Female	9 69.2%	6 50%	15 60%
Male	4 30.8%	6 50%	10 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	0 0%	1 4%
Not Hispanic or Latino	12 92.3%	12 100%	24 96%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 15.4%	3 25%	5 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 7.7%	3 25%	4 16%
White	10 76.9%	6 50%	16 64%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%	12 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Total Sleep Time in the First Two-Thirds of the Night on the Night(s) Most Likely to be Disrupted
Description	Measured using polysomnography (PSG) and analyzed as change from baseline. Examination of the observational phase baseline data demonstrated that Night 3 was the night most disrupted.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [minutes]	76.2 (11.213)	41.4 (11.882)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0354
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	34.75
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Patient Global Impression of Severity (PGI-S) Day 4
Description	Self-reported global index measure analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight. The PGI-S is a single question asking the subject to rate their jet-lag condition at the present time on a scale of 1 "Normal" to 4 "Severe".
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [units on a scale]	-0.71 (0.174)	-0.07 (0.183)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0168
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Total Sleep Time in the First Two-Thirds of the Night (All 3 Nights)
Description	Measured using polysomnography (PSG) and analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight.
Time Frame	3 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [Minutes]	131.4 (35.243)	40.9 (37.774)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0785
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	90.56
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Subjective Total Sleep Time on Night 3
Description	Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [Minutes]	111.9 (23.012)	33.47 (24.555)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0225
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	78.45
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Subjective Sleep Quality Night 3
Description	Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline. Sleep quality was ranked from 1 "Poor" to 5 "Excellent" and was the subscale of the post-sleep questionnaire used to determine subjective sleep quality.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [units on a scale]	1.31 (0.273)	0.36 (0.290)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0198
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Subjective Sleep Latency Night 3
Description	Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [Minutes]	-20.6 (8.39)	6.0 (8.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0347
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-26.55
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Subjective Wake After Sleep Onset Night 3
Description	Measured using the post-sleep questionnaire on Day 4 and analyzed as change from baseline
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [Minutes]	-81.1 (22.53)	-24.7 (24.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	LS mean and p-value are from ANCOVA with treatment and time-zone-shift as main effects and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.0840
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-56.44
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Karolinska Sleepiness Scale Day 4
Description	Self-reported fatigue measure analyzed as change from baseline. The baseline was the corresponding measurement in the screening flight. The KSS is a single question asking the subject to rate how sleepy they feel at that moment on a 9-point scale where 1 = extremely awake and 9 = extremely sleepy/fighting to stay wake.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tasimelteon	Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule	Placebo, administered as oral capsule(s) Placebo: capsule
Measure Participants	13	12
Least Squares Mean (Standard Error) [units on a scale]	-1.69 (0.388)	-0.69 (0.409)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasimelteon, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0765
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	15 months
Arm/Group Title	Tasimelteon		Placebo
Arm/Group Description	tasimelteon, administered as oral capsule(s) Tasimelteon: capsule		Placebo, administered as oral capsule(s) Placebo: capsule
All Cause Mortality
	Tasimelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	Tasimelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Tasimelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/13 (53.8%)		4/12 (33.3%)
Ear and labyrinth disorders
Ear discomfort	1/13 (7.7%)		0/12 (0%)
Gastrointestinal disorders
Vomiting	2/13 (15.4%)		0/12 (0%)
Nausea	0/13 (0%)		1/12 (8.3%)
General disorders
Malaise	0/13 (0%)		1/12 (8.3%)
Infections and infestations
Nasopharyngitis	0/13 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Dehydration	0/13 (0%)		1/12 (8.3%)
Nervous system disorders
Headache	4/13 (30.8%)		4/12 (33.3%)
Skin and subcutaneous tissue disorders
Skin irritation	0/13 (0%)		1/12 (8.3%)

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.