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Name: Iclepertin
Synonyms: BI 425809
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease, Schizophrenia
U.S. FDA Status: Alzheimer's Disease (Discontinued), Schizophrenia (Phase 3)
Company: Boehringer Ingelheim


This compound is a glycine transporter inhibitor that was being develped for the treatment of Alzheimer's disease, then discontinued; it remains in development for schizophrenia. The rationale behind this approach is that abnormalities in glutamatergic signaling downstream of neuronal NMDA receptors contribute to cognitive impairment in both these diseases, hence boosting NMDA receptor function might benefit synaptic plasticity and cognition (Lakhan et al., 2013Rosenbrock et al., 2022). The amino acid neurotransmitter glycine is an obligatory NMDA receptor co-agonist. Glycine transporters GlyT-1 and GlyT-2 located in presynaptic and astrocyte membranes take up glycine into the nerve terminal and adjacent glial cells, thus modulating glycine levels in the synaptic cleft (Hashimoto, 2010). By blocking these receptors, BI 425809 is proposed to increase glycine levels and its ability to modulate NMDA receptor function. No preclinical data related to Alzheimer’s are published on this compound.


In March 2014, Boehringer Ingelheim started up a series of Phase 1 trials—seven as of May 2018—to evaluate the safety, bioavailability, and pharmacokinetics of BI 425809, as well as its potential interactions with commonly used drugs. These trials were conducted in 298 young and elderly men and women in Germany, Belgium, and Korea. Single- and multiple-ascending-dose results were reported as showing BI 425809 to be generally well-tolerated and suitable for once-daily dosing (Moschetti et al., 2016Moschetti et al., 2018). In one multiple-dosing study, healthy volunteers showed a dose-dependent increase in CSF glycine by an average of 50 percent two weeks after the last administration (Rosenbrock et al., 2018). Detailed pharmacokinetic and safety data from a study in 83 healthy men were reported as showing safety and tolerability within the target dose range of up to 25 mg. Higher doses generate adverse events previously reported for glycine reuptake inhibition, such as drowsiness, fatigue, vertigo, blurred vision (Moschetti et al., 2018Hirayasu et al., 2016). Pharmacokinetics and safety were similar in Caucasian, Chinese, and Japanese adults (Tsuda et al., 2019).

In August 2016, a Phase 2 study started comparing 2, 5, 10, or 25 mg daily doses of BI 425809 to placebo, taken for three months, in 610 people with early signs of Alzheimer's dementia. The primary outcome was change on the ADAS-Cog11; secondary outcomes were change on the ADCS-ADL and CIBIC+ scales. The trial made no use of biomarkers. It took place at 27 sites in North America, Austria, Finland, France, Germany, Greece, Hungary, and Spain. The study was completed in October 2019. In February 2020, Boehringer Ingelheim announced that top-line data indicated the trial was negative and that further development for Alzheimer's had stopped (press release). Data presented at the July 2020 AAIC showed that the drug had not improved cognition on any of the primary or secondary measures compared with placebo at any dose. The results were published after peer review (Wunderlich et al., 2023).

For all trials of this compound, see

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034
Boehringer Ingelheim NCT02788513

Last Updated: 06 Feb 2023


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Paper Citations

  1. . First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males. Br J Clin Pharmacol. 2016 Nov;82(5):1315-1324. Epub 2016 Aug 22 PubMed.
  2. . Multiple Rising Doses of Oral BI 425809, a GlyT1 Inhibitor, in Young and Elderly Healthy Volunteers: A Randomised, Double-Blind, Phase I Study Investigating Safety and Pharmacokinetics. Clin Drug Investig. 2018 Aug;38(8):737-750. PubMed.
  3. . Evaluation of Pharmacokinetics and Pharmacodynamics of BI 425809, a Novel GlyT1 Inhibitor: Translational Studies. Clin Transl Sci. 2018 Nov;11(6):616-623. Epub 2018 Aug 23 PubMed.
  4. . Safety, Tolerability and Pharmacokinetics of Oral BI 425809, a Glycine Transporter 1 Inhibitor, in Healthy Male Volunteers: A Partially Randomised, Single-Blind, Placebo-Controlled, First-in-Human Study. Eur J Drug Metab Pharmacokinet. 2018 Apr;43(2):239-249. PubMed.
  5. . A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia. BMC Psychiatry. 2016 Mar 15;16:66. PubMed.
  6. . Pharmacokinetics of Single Doses of BI 425809 in Healthy Chinese and Japanese Subjects: A Randomized Study. Clin Ther. 2019 May;41(5):961-971. Epub 2019 Apr 17 PubMed.
  7. . Efficacy and safety of the novel GlyT1 inhibitor BI 425809 in Alzheimer's dementia: a randomized controlled trial. Alzheimers Res Ther. 2023 Jan 28;15(1):24. PubMed.
  8. . NMDA Receptor Activity in Neuropsychiatric Disorders. Front Psychiatry. 2013;4:52. Epub 2013 Jun 10 PubMed.
  9. . Effects of the Glycine Transporter-1 Inhibitor Iclepertin (BI 425809) on Sensory Processing, Neural Network Function, and Cognition in Animal Models Related to Schizophrenia. J Pharmacol Exp Ther. 2022 Aug;382(2):223-232. Epub 2022 Jun 5 PubMed.
  10. . Glycine transport inhibitors for the treatment of schizophrenia. Open Med Chem J. 2010 May 27;4:10-9. PubMed.

External Citations

  1. press release

Further Reading


  1. . Evaluation of the Efficacy of BI 425809 Pharmacotherapy in Patients with Schizophrenia Receiving Computerized Cognitive Training: Methodology for a Double-blind, Randomized, Parallel-group Trial. Clin Drug Investig. 2020 Apr;40(4):377-385. PubMed.
  2. . Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. J Clin Psychopharmacol. 2023 Jan 26; PubMed.
  3. . Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809). Transl Psychiatry. 2022 Aug 11;12(1):329. PubMed.
  4. . Correction to: The Absolute Bioavailability, Absorption, Distribution, Metabolism, and Excretion of BI 425809 Administered as an Oral Dose or an Oral Dose with an Intravenous Microtracer Dose of [14C]‑BI 425809 in Healthy Males. Clin Drug Investig. 2022 Apr;42(4):375. PubMed.
  5. . New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Neurosci Biobehav Rev. 2022 Jan;132:324-361. Epub 2021 Nov 24 PubMed.
  6. . Effects of Cytochrome P450 3A4 Induction and Inhibition on the Pharmacokinetics of BI 425809, a Novel Glycine Transporter 1 Inhibitor. Eur J Drug Metab Pharmacokinet. 2022 Jan;47(1):91-103. Epub 2021 Oct 29 PubMed.
  7. . Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry. 2021 Mar;8(3):191-201. PubMed.