Healthy Participants and Patients With Narcolepsy Clinical Trial
Official title:
A Phase 1 Study of TAK-925 to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of TAK-925 in Healthy Adult and Elderly Volunteers and Patients With Narcolepsy
| Verified date | March 2021 |
| Source | Takeda |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to investigate safety, tolerability, and pharmacokinetics of TAK-925 when a single dose of TAK-925 is administered to healthy adult participants, healthy elderly participants and patients with type 1 narcolepsy.
| Status | Completed |
| Enrollment | 58 |
| Est. completion date | September 4, 2018 |
| Est. primary completion date | September 4, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | Inclusion Criteria: Healthy adult participants and Healthy elderly participants: - Participant weighs at least 50 kilogram (kg) (Healthy adults participants) / 40 kg (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 kilogram per square meter (kg/m^2), inclusive at Screening. Narcolepsy patients: - Patient weighs at least 40 kg inclusive at Screening. - A diagnosis of narcolepsy Type 1, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3). - HLA narcolepsy test positivity. - At Day -1, Epworth sleepiness scale (ESS) score greater than or equal to (>=) 10 - Blood pressure less than (<) 140 systolic and < 90 diastolic. The patient may have a history of hypertension and be on antihypertensive medication treatment as long as the BP meets these criteria. Exclusion Criteria: All Participants: - Participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit. - Past or current epilepsy, convulsion, tremor or the disorders of related symptoms. - Has a lifetime history of major psychiatric disorder, such as major depressive disorder, bipolar disorder, or schizophrenia. HV (only Cohort 4): - Participant has had CSF collection performed within 14 days prior to check-in (Day -1). Narcolepsy patients - Medical disorder associated with excessive sleepiness other than narcolepsy (including sleep apnea syndrome). - Excessive caffeine (greater than [>] 400 milligram per day [mg/day]) use one week prior to study. |
| Country | Name | City | State |
|---|---|---|---|
| Japan | Hakata Clinic | Fukuoka | |
| Japan | PS Clinic | Fukuoka | |
| Japan | Sumida Hospital | Sumida-ku | Tokyo |
| Lead Sponsor | Collaborator |
|---|---|
| Takeda |
Japan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 7 | ||
| Primary | Number of Participants Who Experience at Least One TEAE Related to Vital Signs | Baseline up to Day 7 | ||
| Primary | Number of Participants Who Experience at Least One TEAE Related to Body Weight | Baseline up to Day 7 | ||
| Primary | Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG) | Baseline up to Day 7 | ||
| Primary | Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests | Baseline up to Day 7 | ||
| Primary | Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, CL: Total Clearance After Intravenous Administration for TAK-925 | Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion | ||
| Primary | Part 2, CL: Total Clearance After Intravenous Administration for TAK-925 | Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion | ||
| Primary | Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion | |
| Primary | Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion | |
| Primary | Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2 | Urine assessments were done only in Part 1, as planned. | Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion | |
| Primary | Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4 | Day 1 at 6 hours after start of infusion | ||
| Secondary | Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT) | The MWT is a validated objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period of time. This tendency to fall asleep is measured via electroencephalography-derived sleep latency. Sleep onset is defined as the first epoch of greater than 15 seconds of cumulative sleep in a 30-second epoch. Trials were ended after 40 minutes if no sleep occurs, or after unequivocal sleep, defined as 3 consecutive epochs of stage 1 sleep, or 1 epoch of any other stage of sleep. If no sleep has been observed according to these rules, then the latency is defined as 40 minutes. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake. | Days 1 and 3 up to 8 hours following the start of infusion |