pitolisant
Trade name: Wakix
Approved
Aug 14, 2019
Pitolisant (INN) or tiprolisant (USAN) is a histamine receptor inverse agonist/antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies and may have several medical applications, having been researched for the treatment of narcolepsy, for which it has been granted orphan drug status in the EU and US. It is currently in clinical trials for schizophrenia and Parkinson’s disease. Pitolisant hydrochloride was approved by European Medicine Agency (EMA) on Mar 31, 2016. It was developed and marketed as Wakix® by Bioprojet in EU. Wakix® is available as the tablet for oral use, containing 4.5 mg and 18 mg of Pitolisant hydrochloride. The initial dose of 9 mg (two 4.5 mg, tablets) per day, and it should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day. Pitolisant was the first clinically used H3 receptor inverse agonist. — NCATS
Clinical trial activity
34 trials · 15 clinical orgs · 2 marketing orgs
Earliest trial started Oct 1, 2007 (NCT00642928)
Timeline
2000s
2010s
- May 17, 2010
Orphan Drug Designation
- Jan 1, 2011
- Aug 14, 2019
Bioprojet — Earliest FDA Approval
- Aug 14, 2019
Harmony Biosciences, LLC — Marketing Organization
- Aug 14, 2019
Bioprojet — NDA Organization
- Aug 14, 2019
Harmony Biosciences, LLC — NDA Secondary Org
Indications
Approved for
Studied for
- Alcohol Drinking · Phase 1
- Alcohol-Induced Disorders, Nervous System · Phase 2
- Alcoholism · Phase 1
- Autism Spectrum Disorder · Phase 2
- Cataplexy · Phase 3
- Diabetes Mellitus, Type 1 · Phase 1
- Disorders of Excessive Somnolence · Phase 3
- Healthy Volunteers · Phase 1
- Hypoglycemia · Phase 1
- Idiopathic Hypersomnia · Phase 3
- Kidney Failure, Chronic · Phase 1
- Myotonic Dystrophy · Phase 2
- Narcolepsy · Phase 3
- Parkinson Disease · Phase 3
- Prader-Willi Syndrome · Phase 3
- Restless Legs Syndrome · Phase 4
- Schizophrenia · Phase 2
- Sleep Apnea, Obstructive · Phase 3
- Sleep Disorders, Intrinsic · Phase 3
- Sleep Wake Disorders · Phase 3
- Substance-Related Disorders · Phase 1
Mechanism of action
- Histamine H3 receptorINVERSE AGONIST
HRH3 inverse agonist
Approval history
- approvedPriority reviewFast trackAug 14, 2019
Chemistry & pharmacology
SMILES
ClC1=CC=C(CCCOCCCN2CCCCC2)C=C1- Mol. weight
- 295.847 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
No
Sources
- WikipediaPitolisant ↗
- NCATS4BC83L4PIY ↗
- ChEMBLCHEMBL462605 ↗
- ChEMBLCHEMBL4164059 ↗
Also known as
- 1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine
- b.249
- bf 2.649
- bf 2.649
- bf2.649
- bf2.649
- bf2.649
- bf2.649
- modiodal
- pitolisant
- pitolisant
- pitolisant
- pitolisant
- pitolisant
- pitolisant
- pitolisant
- pitolisant hydrochloride
- tiprolisant
- tiprolisant
- tiprolisant
- tiprolisant
- tiprolisant hydrochloride
- wakix
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07219485 | Phase 3 | Aug 20, 2025 | Harmony Biosciences, LLC |
| NCT07051252 | Phase 1 | May 21, 2025 | Harmony Biosciences, LLC |
| NCT06366464 | Phase 3 | May 28, 2024 | Harmony Biosciences, LLC |
| NCT05953389 | Phase 2 | Oct 31, 2023 | Bioprojet |
| NCT05849675 | N/A | Apr 1, 2023 | University of Oxford |
| NCT05581576 | Phase 4 | Sep 20, 2022 | Harmony Biosciences, LLC, The University of Texas, Dallas |
| NCT05458128 | Phase 3 | Aug 19, 2022 | Harmony Biosciences, LLC |
| NCT05156047 | Phase 3 | Jun 30, 2022 | Harmony Biosciences, LLC |
| NCT05223166 | Phase 3 | Apr 12, 2022 | Citrine Medicine Limited |
| NCT04886518 | Phase 2 | Jun 28, 2021 | Harmony Biosciences, LLC |
| NCT04596267 | Phase 1 | Feb 28, 2021 | Boston University, National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
| NCT04257929 | Phase 2 | Apr 30, 2020 | Harmony Biosciences, LLC |
| NCT04026750 | Phase 1 | Jun 19, 2019 | Ferox Therapeutics, High Point Clinical Trial Center |
| NCT03152123 | Phase 1 | Mar 15, 2017 | Bioprojet, INC Research |
| NCT02978651 | Phase 3 | Jan 1, 2017 | Bioprojet |
| NCT02800083 | Phase 2 | Oct 1, 2016 | Bioprojet |
| NCT02929342 | Phase 1 | Jul 1, 2016 | Bioprojet, Quotient |
| NCT02739568 | Phase 3 | Apr 1, 2016 | Bioprojet |
| NCT02611687 | Phase 2 | Apr 1, 2016 | Bioprojet |
| NCT01800045 | Phase 3 | Apr 1, 2013 | Bioprojet |
Organizations
Research & Development (15)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Bioprojet | For profit | 21 | 20 | 3 | 2007 |
| Harmony Biosciences, LLC | For profit | 9 | 8 | 5 | 2020 |
| Neurocenter of Southern Switzerland, Lugano | Academic/Hospital | 2 | 0 | 1 | 2009 |
| The University of Texas, Dallas | Academic/Hospital | 2 | 2 | 2 | 2008 |
| Boston University | Academic/Hospital | 1 | 1 | 1 | 2021 |
| Citrine Medicine Limited | For profit | 1 | 1 | 1 | 2022 |
| Ferox Therapeutics | For profit | 1 | 0 | 1 | 2019 |
| High Point Clinical Trial Center | For profit | 1 | 1 | 1 | 2019 |
| INC Research | For profit | 1 | 0 | 1 | 2017 |
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Government | 1 | 0 | 1 | 2021 |
| Quotient | For profit | 1 | 0 | 1 | 2016 |
| Stanley Medical Research Institute | Academic/Hospital | 1 | 0 | 1 | 2008 |
| University of Lyon | Academic/Hospital | 1 | 0 | 1 | 2011 |
| University of Oxford | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Yeshiva University | Academic/Hospital | 1 | 0 | 1 | — |
Marketing (3)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Bioprojet | For profit | NDA | Aug 14, 2019 |
| Harmony Biosciences, LLC | For profit | MKTG | Aug 14, 2019 |
| Harmony Biosciences, LLC | For profit | NDA2 | Aug 14, 2019 |