Trial Outcomes & Findings for Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™) (NCT NCT02130999)

NCT ID: NCT02130999

Last Updated: 2016-08-22

Results Overview

The absolute bioavailability (F) of tasimelteon will be estimated from the dose-corrected AUC(inf) after oral and I.V. administration using an analysis of variance (ANOVA) model with treatment, period, sequence, and subject within sequence as the classification variables, using natural log-transformed data. The geometric mean ratio (GMR), oral-to-I.V., and its associated 90% confidence interval (CI) will be used as the estimate of F and its variability.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 14 participants
• Primary outcome timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
• Results posted on: 2016-08-22

Participant Flow

Participant milestones

Measure	Sequence A * Single oral dose of tasimelteon 20 mg on Day 1 * Single I.V. dose of tasimelteon 2 mg on Day 6 tasimelteon 20 mg capsule tasimelteon 2 mg I.V.	Sequence B * Single I.V. dose of tasimelteon 2 mg on Day 1 * Single oral dose of tasimelteon 20 mg on Day 6 tasimelteon 20 mg capsule tasimelteon 2 mg I.V.
Overall Study STARTED	6	8
Overall Study COMPLETED	6	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Open Label Study to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™)

Baseline characteristics by cohort

Measure	Overall Number of Baseline Participants n=14 Participants 14 subjects total participated in the study
Age, Continuous	31.2 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants
Body Mass Index	22.8 (kg/m^2) STANDARD_DEVIATION 1.8 • n=5 Participants
Weight	63.6 (kg) STANDARD_DEVIATION 8 • n=5 Participants
Height	166.6 (cm) STANDARD_DEVIATION 10.4 • n=5 Participants

PRIMARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

The absolute bioavailability (F) of tasimelteon will be estimated from the dose-corrected AUC(inf) after oral and I.V. administration using an analysis of variance (ANOVA) model with treatment, period, sequence, and subject within sequence as the classification variables, using natural log-transformed data. The geometric mean ratio (GMR), oral-to-I.V., and its associated 90% confidence interval (CI) will be used as the estimate of F and its variability.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg)	All Subjects
Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg	38.3 Geometric Mean Ratio (%) Interval 26.9 to 54.3	—	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

Cmax of tasimelteon will be compared when given orally or administered as an I.V.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.	260 ng/mL Standard Deviation 189	82.2 ng/mL Standard Deviation 20.5	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

AUC (inf) of Tasimelteon will be compared when given orally or administered as an I.V.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.	358 (h*ng/mL) Standard Deviation 271	71.6 (h*ng/mL) Standard Deviation 23.9	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours pos-dose

T1/2 of tasimelteon will be compared when given orally or administered as an I.V.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.	1.06 hour Standard Deviation 0.23	1.02 hour Standard Deviation 0.23	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

CL of tasimelteon will be compared when given orally or administered as an I.V.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.	2241 (mL/min) Standard Deviation 3592	505 (mL/min) Standard Deviation 135	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

The mean +/- SD for the Cmax of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon M9	303 ng/mL Standard Deviation 94.3	16.4 ng/mL Standard Deviation 6.16	—
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon M11	53.2 ng/mL Standard Deviation 16.14	3.7 ng/mL Standard Deviation 1.25	—
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon M12	113 ng/mL Standard Deviation 30.8	7.31 ng/mL Standard Deviation 2.49	—
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon M13	370 ng/mL Standard Deviation 105	29 ng/mL Standard Deviation 11.7	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

Population: Only 11 subjects could be analyzed for M11.

The mean +/- SD for the AUC(inf) of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose M9	400 h*ng/mL Standard Deviation 139	30.3 h*ng/mL Standard Deviation 10.3	—
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose M11	125 h*ng/mL Standard Deviation 43.7	12.2 h*ng/mL Standard Deviation 4.40	—
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose M12	619 h*ng/mL Standard Deviation 364	43.8 h*ng/mL Standard Deviation 25.4	—
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose M13	431 h*ng/mL Standard Deviation 152	38.2 h*ng/mL Standard Deviation 13	—

SECONDARY outcome

Timeframe: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose

Comparison of the metabolite-to-parent AUC(inf) ratios for the oral and IV routes.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon M9	1.98 metabolite to parent AUC (inf) ratios Standard Deviation 2.65	0.39 metabolite to parent AUC (inf) ratios Standard Deviation 0.12	—
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon M11	0.51 metabolite to parent AUC (inf) ratios Standard Deviation 0.35	0.16 metabolite to parent AUC (inf) ratios Standard Deviation 0.03	—
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon M12	2.04 metabolite to parent AUC (inf) ratios Standard Deviation 0.93	0.54 metabolite to parent AUC (inf) ratios Standard Deviation 0.15	—
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon M13	1.72 metabolite to parent AUC (inf) ratios Standard Deviation 1.12	0.51 metabolite to parent AUC (inf) ratios Standard Deviation 0.14	—

SECONDARY outcome

Timeframe: From Baseline to End of Study; Day 5 (± 2 days).

Number of participants with treatment-emergent adverse event per treatment arm and overall.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects n=14 Participants
Number of Participants With Adverse Events vomiting	0 participants	1 participants	1 participants
Number of Participants With Adverse Events headache	1 participants	1 participants	2 participants
Number of Participants With Adverse Events Somnolance	1 participants	0 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to End of Study Day 5 (± 2 days).

Number of Participants that reported suicidal ideation, suicidal behavior, or suicide attempts per treatment arm and overall.

Outcome measures

Measure	Absolute Bioavailability n=14 Participants	IV (2 mg) n=14 Participants	All Subjects n=14 Participants
Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts.	0 participants	0 participants	0 participants

Adverse Events

Tasimelteon 20mg Oral

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Tasimelteon 2mg IV

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

All Subjects

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Tasimelteon 20mg Oral n=14 participants at risk	Tasimelteon 2mg IV n=14 participants at risk	All Subjects n=14 participants at risk
Nervous system disorders headache	7.1% 1/14	7.1% 1/14	14.3% 2/14
Nervous system disorders sommolence	7.1% 1/14	0.00% 0/14	7.1% 1/14
Gastrointestinal disorders vomiting	0.00% 0/14	7.1% 1/14	7.1% 1/14

Additional Information

Melodie Armstrong, MD, MPH

Vince and Associates Clinical Research

Phone: 913-696-1601

Results disclosure agreements

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

Restriction type: GT60