Clinical trial • Phase II/III • Neurology

N-{(2S,3R)-4,4-DIFLUORO-1-(2-HYDROXY-2-METHYLPROPANOYL)-2-[(2,3',5'-TRIFLUORO[1,1'-BIPHENYL]-3-YL)METHYL]PYRROLIDIN-3-YL}ETHANESULFONAMIDE for Narcolepsy Type 1

Phase II/III trial of N-{(2S,3R)-4,4-DIFLUORO-1-(2-HYDROXY-2-METHYLPROPANOYL)-2-[(2,3',5'-TRIFLUORO[1,1'-BIPHENYL]-3-YL)METHYL]PYRROLIDIN-3-YL}ETHANESULFO…

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Narcolepsy Type 1
Trial Stage
Phase II/III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
24-01-2024
First CTIS Authorization Date
27-03-2024

Trial design

Randomised, tak-861 placebo (same excipients as tak-861); dose/schedule not specified-controlled, adaptive Phase II/III trial in Sweden, Germany, Austria and others.

Randomised
Yes
Comparator
TAK-861 placebo (same excipients as TAK-861); dose/schedule not specified
Adaptive
True; blinded initial study treatment assignment and subsequent dose changes are managed using IRT; participants from some parent trials will be re-randomized to one of available dose regimens (assigned dose may be same, one level lower or one level higher), and participants randomized to placebo in parent trials will be randomized to dose regimens in this extension.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
158
Trial Duration For Participant
1825

Eligibility

Recruits 158 adults.

Inclusion criteria

  • {"criterion_text":"- Participant with a diagnosis of NT1 who has completed a controlled Trial with TAK-861, who meet all inclusion criteria and does not meet any exclusion criteria, and for whom the investigator has no clinical objection to their enrollment."}

Exclusion criteria

  • {"criterion_text":"- Participant has a treatment-related adverse event (TEAE) that remains severe at the time of rollover related to the study drug from the parent study or discontinued because of TEAEs in the parent study."}
  • {"criterion_text":"- Participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), or cerebral hemorrhage."}
  • {"criterion_text":"- Participant has a history of myocardial infarction, clinically significant coronary artery disease, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure."}
  • {"criterion_text":"- Participant has a history of cancer in the past 5 years (does not apply to participants with carcinoma in situ that has been resolved without further treatment, or basal cell skin cancer; these participants may be included after approval by the sponsor or designee)."}
  • {"criterion_text":"- The participant has a positive urine screen result for drugs of abuse and/or positive alcohol test result at screening or at Day -2 if a dosing gap > 7 days is present. An exception at screening is made for stimulants or other drugs the participant has been prescribed."}
  • {"criterion_text":"- Participant has a risk of suicide according to endorsement of item 4 or 5 on the Columbia Suicide Severity Rating Scale Since Last Visit (C-SSRS) on any visit in the prior study or has positive answers on item 4 or 5 on the C-SSRS Screening/Baseline (based on the past year) during the screening assessment for participants with a dosing gap."}
  • {"criterion_text":"- Participant has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 times the upper limit of normal (ULN) at multiple visits in the parent study and the findings are of clinical significance, per investigator or sponsor opinion, or ALT/AST >1.5 times ULN during the screening period for participants with a dosing gap."}
  • {"criterion_text":"- Participant has a current medical disorder, other than narcolepsy with or without cataplexy, associated with excessive daytime sleepiness (EDS)."}
  • {"criterion_text":"- Participant has current active major depressive episode (MDE) or has had an active MDE in the past 6 months."}
  • {"criterion_text":"- Participant has developed (within the last 6 months) gastrointestinal disease that is expected to influence the absorption of drugs (i.e., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention)."}
  • {"criterion_text":"- Participant has epilepsy or history of seizure."}
  • {"criterion_text":"- Participant has any other medical condition, such as anxiety, depression, heart disease, or significant hepatic, pulmonary, or renal disease, that requires them to take excluded medications."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Occurrence of at least 1 treatment-emergent adverse event (TEAE).","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in the parent study in MWT mean sleep latency.","definition_or_measurement_approach":"Change from baseline in the parent study measured by the Maintenance of Wakefulness Test (MWT) mean sleep latency."}
  • {"endpoint_text":"- Change from baseline in the parent study in ESS total score","definition_or_measurement_approach":"Change from baseline in the parent study measured by the Epworth Sleepiness Scale (ESS) total score."}
  • {"endpoint_text":"- Change from baseline in the parent study in WCR using the patient reported Cataplexy Diary","definition_or_measurement_approach":"Change from baseline in the parent study in weekly cataplexy rate (WCR) assessed using the patient-reported Cataplexy Diary."}

Recruitment

Digital Remote Recruitment
True; patient invitation letters/emails and transition flyers are included as recruitment materials (country-specific email invitation documents listed).
Planned Sample Size
158
Recruitment Window Months
60
Consent Approach
Informed consent is managed using country-specific Main ICF documents (multiple Main ICF files listed for Sweden, Germany, Italy, Belgium, Netherlands, France, Spain, Finland, Norway, Poland, Austria). Additional ICFs include pregnant participant ICFs, pregnant partner ICFs, healthy volunteer ICFs, home health care ICFs, optional future research ICFs, and a newborn ICF (France). Consent is obtained using local-language, country-specific ICFs; documents are available in multiple languages corresponding to trial countries (e.g., EN, DE, FR, IT, ES, NL, PL, FI, NO, SE).

Methods

  • Patient Invitation Letter / Email (country-specific patient invitation letters present in documents)
  • Transition flyer (study transition flyers used to inform eligible participants)
  • Recruitment arrangements documents (country-specific K1 recruitment arrangements)

Geography

Total Number Of Sites
33
Total Number Of Participants
304

Sweden

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
745
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Uppsala University Hospital
Department Name
VO Neuro
Contact Person Name
Valter Niemelä
Contact Person Email
valter.niemela@neuro.uu.se

Germany

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
746
Number Of Sites
3
Number Of Participants
14

Sites

Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Schlafmedizinisches Zentrum Klinik und Poliklinik für Psychiatrie und Psychotherapie
Contact Person Name
Renata Almeida Schreck
Contact Person Email
renata.almeidaschreck@medbo.de
Site Name
Advanced Sleep Research GmbH
Contact Person Name
Katharina Lederer
Site Name
Somni bene Institut fuer medizinische Forschung und Schlafmedizin Schwerin GmbH
Contact Person Name
Heiike Beneš
Contact Person Email
heike.benes@somnibene.de

Austria

Earliest CTIS Part Ii Submission Date
31-01-2025
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
388
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Johannes Kepler University Linz
Department Name
Neuromed Campus
Contact Person Name
Andreas Kaindlstorfer

Belgium

Earliest CTIS Part Ii Submission Date
24-01-2025
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
395
Number Of Sites
5
Number Of Participants
11

Sites

Site Name
Anima
Department Name
Sleep Department
Contact Person Name
Erik Buntinx
Contact Person Email
Erik.buntinx@anima-alken.be
Site Name
UZ Leuven
Department Name
Sleep Department
Contact Person Name
Dries Testelmans
Contact Person Email
Dries.testelmans@uzleuven.be
Site Name
Centre Hospitalier Regional De La Citadelle
Department Name
Sleep Department
Contact Person Name
Farhad Baharloo
Site Name
Universitair Ziekenhuis Gent
Department Name
Department Neurology
Contact Person Name
Stephanie Hödl
Contact Person Email
Stephanie.Hoedl@uzgent.be
Site Name
Pneumocare
Department Name
Sleep Department
Contact Person Name
Jean-Benoît Martinot
Contact Person Email
Martinot.j@respisom.be

Netherlands

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
746
Number Of Sites
1
Number Of Participants
9

Sites

Site Name
Epilepsie Instellingen Nederland Stichting
Contact Person Name
G.J. Lammers
Contact Person Email
GJLammers@sein.nl

Italy

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
23-02-2026
Processing Time Days
745
Number Of Sites
3
Number Of Participants
75

Sites

Site Name
Istituto Neurologico Mediterraneo Neuromed S.p.A.
Department Name
Centro Medicina del Sonno
Principal Investigator Name
Andrea Romigi
Principal Investigator Email
andrea.romigi@neuromed.it
Contact Person Name
Andrea Romigi
Contact Person Email
andrea.romigi@neuromed.it
Site Name
Ospedale Bellaria - Azienda USL di Bologna
Department Name
IRCCS Istituto delle Scienze Neurologiche
Principal Investigator Name
Giuseppe Plazzi
Principal Investigator Email
giuseppe.plazzi@unibo.it
Contact Person Name
Giuseppe Plazzi
Contact Person Email
antonella.mura@ausl.bologna.it
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
UOC Neurologia
Principal Investigator Name
Claudio Liguori
Principal Investigator Email
dott.claudioliguori@yahoo.it
Contact Person Name
Claudio Liguori
Contact Person Email
dott.claudioliguori@yahoo.it

Norway

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
24-02-2026
Processing Time Days
746
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Oslo University Hospital HF
Department Name
Department of Neurology
Contact Person Name
Kristian Nilsen
Site Name
Helse Bergen HF
Department Name
Nevroklinikken
Contact Person Name
Henning Olberg

France

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
752
Number Of Sites
7
Number Of Participants
85

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service des pathologies du sommei
Contact Person Name
Isabelle ARNULF
Contact Person Email
isabelle.arnulf@aphp.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service de Neurologie Boulevard Professeur Jacques Monod
Contact Person Name
Laurène LECLAIR-VISONNEAU
Contact Person Email
laurene.leclair@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Unité des Troubles du Sommeil Service de Neurologie
Contact Person Name
Yves Dauvilliers
Site Name
Centre Hospitalier Universitaire De Toulouse
Contact Person Name
Rachel Debs
Contact Person Email
debs.r@chu-toulouse.fr
Site Name
Hospices Civils De Lyon
Department Name
Centre de médecine du sommeil
Contact Person Name
Laure PETER-DEREX
Contact Person Email
laure.peter-derex@chu-lyon.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service de l’épileptologie et de la rythmologie cérébrale
Contact Person Name
Isabelle LAMBERT
Contact Person Email
isabelle.lambert@ap-hm.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service de Médicine de Sommeil
Contact Person Name
Pierre PHILIP
Contact Person Email
pierre.philip@chu-bordeaux.fr

Finland

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
05-03-2026
Processing Time Days
755
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Suomen Terveystalo Oy
Department Name
Terveystalo Helsinki Sleep Clinic
Contact Person Name
Gabriele Sved
Contact Person Email
gabriele.sved@terveystalo.com
Site Name
Tampere University Hospital
Department Name
Dept of Neurological Specialties
Contact Person Name
Tomi Sarkanen
Contact Person Email
tomi.sarkanen@pirha.fi

Spain

Earliest CTIS Part Ii Submission Date
09-02-2024
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
764
Number Of Sites
7
Number Of Participants
85

Sites

Site Name
Hospital Universitario De La Ribera
Department Name
Neurophysiology and sleep disorders unit
Contact Person Name
Francisco Puertas Cuesta
Contact Person Email
puertas_jav@gva.es
Site Name
Hospital Universitario Araba
Department Name
Funtional sleep unit
Contact Person Name
Ainhoa Alvarez Ruiz de Larrinaga
Contact Person Email
ainhoaarl@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Neurophysiology
Contact Person Name
Odile Romero Santo-Tomás
Contact Person Email
oromerosanto1963@gmail.com
Site Name
Hospital Nuestra Senora De America
Department Name
Neurophysiology and sleep disorders unit
Principal Investigator Name
Rafael Del Río Villegas
Principal Investigator Email
puertas_jav@gva.es
Contact Person Name
Rafael Del Río Villegas
Contact Person Email
puertas_jav@gva.es
Site Name
Hospital General Universitario De Castellon
Department Name
Sleep unit
Contact Person Name
Raquel Lopez Garcia
Contact Person Email
lopezraqgar@gva.es
Site Name
Hospital Clinic De Barcelona
Department Name
Neurology
Principal Investigator Name
Alejandro Iranzo de Riquer
Principal Investigator Email
airanzo@clinic.cat
Contact Person Name
Alejandro Iranzo de Riquer
Contact Person Email
airanzo@clinic.cat
Site Name
Hospital Universitari Vall D Hebron (duplicate listed?)
Department Name
Neurophysiology
Contact Person Name
Odile Romero Santo-Tomás
Contact Person Email
oromerosanto1963@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
19-02-2025
Latest Decision Or Authorization Date
05-05-2026
Processing Time Days
440
Number Of Sites
1
Number Of Participants
6

Sites

Site Name
Linden Sp. z o.o. sp.k.
Contact Person Name
Jakub Antczak
Contact Person Email
rejestracja@cmlinden.com

Sponsor

Primary sponsor

Full Name
Takeda Development Center Americas Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Marken LLP
Responsibilities
Drug shipment from site to subject's home
Name
Clinilabs Inc.
Responsibilities
PSG, MWT
Name
PPD Global Central Labs
Name
PPD Development LP
Responsibilities
PK
Name
WCG Clinical Inc.
Responsibilities
Site staffing & DMC
Name
Pharmaceutical Product Development LLC

Third parties

  • {"country":"United States","full_name":"Marken LLP","duties_or_roles":"Drug shipment from site to subject's home","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/review","organisation_type":"Pharmaceutical company"}
  • {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"Cognitive Testing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eCTP","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Clinilabs Inc.","duties_or_roles":"PSG, MWT","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Site staffing & DMC","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
TAK-861
Active Substance
N-{(2S,3R)-4,4-DIFLUORO-1-(2-HYDROXY-2-METHYLPROPANOYL)-2-[(2,3',5'-TRIFLUORO[1,1'-BIPHENYL]-3-YL)METHYL]PYRROLIDIN-3-YL}ETHANESULFONAMIDE
Modality
Small molecule
Routes Of Administration
Oral
Route
ORAL USE
Authorisation Status
Authorised
Orphan Designation
Yes
Investigational Product Name
TAK-861 placebo (same excipients as TAK-861)
Modality
Other

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