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Phase 1 TAK-925 Study in Healthy Adult and Elderly Volunteers and Patients With Narcolepsy

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ClinicalTrials.gov Identifier: NCT03332784
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Participants and Patients With Narcolepsy Drug: TAK-925 Drug: Placebo Phase 1

Detailed Description:

Orexins are neuropeptides that play a role in the regulation of sleep and wakefulness. In type 1 narcolepsy, there is a loss of orexin producing neurons in the brain. The investigational drug, TAK-925, is an orexin 2 receptor agonist that is being tested in healthy adult participants, healthy elderly participants and patients with narcolepsy in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single intravenous administration.

The study will enroll approximately 20 healthy participants and 16 healthy elderly participants in Part 1 of the study and approximately 20 patients with narcolepsy in Part 2.

In Part 1, the study consists of 4 cohorts of 8 or 4 participants each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the following treatment groups to receive TAK-925 or placebo:

- Part 1, Cohort 1; TAK-925 (Dose Level 1, 3, 5), Cohort 2; TAK-925 (Dose Level 2, 4, 6), Cohort 3 and 4; TAK-925 (Dose Level 5)

For Cohort 1-4, healthy adult and elderly participants will be administered TAK-925 or placebo once in each cohort or dose level. The dose at the start (Cohort 1 dose level 1) is 7 mg of TAK-925 and following doses in Cohorts 1-4 will be determined based on available data from previous Cohorts/dose levels.

In Part 2 of the study, the study consists of 3 cohorts of 4 to 12 patients with narcolepsy. Patients will be randomly assigned to one of the treatment groups of Cohort 5-7 and will be administered TAK-925 or placebo once in each cohort. The dose of TAK-925 in Cohort 5-7 is TBD and will be decided based on available data from Part 1 and previous Cohorts.

- Part 2, Cohort 5-7

This multi-center trial will be conducted in Japan. Participants will make multiple visits to the clinic. Visits in Part 1 will include a screening period (Day -28 to -2), Check-in on Day -1, Treatment period (Day 1 and 2), and follow-up visit on Day 7. In Part 2 of the study, the visits include a screening period (Day -42 to -2), Check-in on Day -1, Cross-over period (Day 1 to 4), and follow-up visit on Day 7.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: A First-in-Human, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-925 in Healthy Adult and Elderly Volunteers and Patients With Narcolepsy
Actual Study Start Date : November 3, 2017
Estimated Primary Completion Date : September 26, 2018
Estimated Study Completion Date : September 26, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: TAK-925 (Cohort 1; Dose Level 1)
TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 2; Dose Level 2)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 1; Dose Level 3)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 2; Dose Level 4)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 1; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 2; Dose Level 6)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Placebo Comparator: Part 1: Placebo (Cohort 1-2)
TAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
Drug: Placebo
TAK-925 Placebo Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 3; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Placebo Comparator: Part 1: Placebo (Cohort 3)
TAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner.
Drug: Placebo
TAK-925 Placebo Intravenous Infusion

Experimental: Part 1: TAK-925 (Cohort 4; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner.
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 2: TAK-925 TBD (Cohort 5)
TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 2: TAK-925 TBD (Cohort 6)
TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Drug: TAK-925
TAK-925 Intravenous Infusion

Experimental: Part 2: TAK-925 TBD (Cohort 7)
TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Drug: TAK-925
TAK-925 Intravenous Infusion

Placebo Comparator: Part 2: Placebo (Cohort 5-7)
TAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
Drug: Placebo
TAK-925 Placebo Intravenous Infusion




Primary Outcome Measures :
  1. Number of Participants who Experience at Least One Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Baseline up to Day 7 ]
  2. Number of Participants who Experience at Least One TEAE Related to Vital Signs [ Time Frame: Baseline up to Day 7 ]
  3. Number of Participants who Experience at Least One TEAE Related to 12-lead electrocardiogram (ECG) [ Time Frame: Baseline up to Day 7 ]
  4. Number of Participants who Experience at Least One TEAE Related to Clinical Laboratory Tests [ Time Frame: Baseline up to Day 7 ]
  5. Cmax: Maximum Observed Plasma Concentration for TAK-925 in Part 1 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  6. Cmax: Maximum Observed Plasma Concentration for TAK-925 in Part 2 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  7. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 in Part 1 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  8. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 in Part 2 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  9. AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-925 in Part 1 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  10. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 in Part 1 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  11. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 in Part 2 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  12. Ae(24): Amount of TAK-925 Excreted in Urine from Time 0 to Time 24 in Part 1 [ Time Frame: Pre-dose, at multiple time points (up to 9 hours) after start of infusion, and at multiple time points (up to 15 hours) after end of infusion ]
  13. R(CSF/Plasma,SS): Cerebrospinal Fluid Drug Concentrations/ Plasma Concentration at the End of Infusion at Steady State for TAK-925 in Cohort 4, Part 1 [ Time Frame: 6 hours after start of infusion ]

Secondary Outcome Measures :
  1. Average Sleep Latency in Maintenance of Wakefulness Test (MWT) in Part 2 [ Time Frame: Days 1 and 3 ]
    MWT uses electroencephalography to measure the time a patient is able to remain awake, providing objective information about the patient's ability to sustain wakefulness.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy adult participants and Healthy elderly participants:

- Participant weighs at least 50 kg (Healthy adults participants) / 40 kg (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 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 ≥10
  • Blood pressure <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, seizure, 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 (>400mg/day) use one week prior to study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332784


Contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

Locations
Japan
Sumida Hospital Recruiting
Sumida-ku, Tokyo, Japan
Hakata Clinic Recruiting
Fukuoka, Japan
PS Clinic Recruiting
Fukuoka, Japan
Sponsors and Collaborators
Takeda
Investigators
Study Director: Study Director Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03332784     History of Changes
Other Study ID Numbers: TAK-925-1001
U1111-1201-6634 ( Other Identifier: WHO )
JapicCTI-173756 ( Registry Identifier: JapicCTI )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
URL: http://

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Narcolepsy
Disorders of Excessive Somnolence
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders