Purity: > 98%
Cebranopadol(GRT-6005) is a novel first in class compounds with potent agonist activity on ORL-1 (opioid receptor like -1) and the well established mu opioid receptor. Cebranopadol and GRT 6006 are novel first-in-class compounds with unique pharmacological and pharmacokinetic profiles that may enhance their effect in certain pain conditions. The unique mode of action of these compounds builds on the ORL-1 receptor and, supported by the established mu opioid receptor, is particularly suitable for the treatment of moderate to severe chronic pain.
1. Eur J Pain. 2018 Oct 26. doi: 10.1002/ejp.1331. [Epub ahead of print]
Cancer-related chronic pain: investigation of the novel analgesic drug candidate
cebranopadol in a randomized, double-blind, non-inferiority trial.
Eerdekens MH(1), Kapanadze S(1), Koch ED(1), Kralidis G(1), Volkers G(1),
Ahmedzai SH(2), Meissner W(3).
(1)Grünenthal GmbH, Aachen, Germany.
(2)Department of Oncology, University of Sheffield, Sheffield, United Kingdom.
(3)Department of Palliative Care, Jena University Hospital, Jena, Germany.
BACKGROUND: Cancer-related pain is a growing health problem given the increasing
life expectancy of cancer patients. Opioids are commonly used to treat
cancer-related pain, but carry the risk of severe side effects, limiting their
use. Cebranopadol is a first-in-class drug candidate, combining
nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial
examined the analgesic efficacy of cebranopadol compared with morphine prolonged
release (PR) in patients with moderate to severe cancer-related pain.
METHODS: This double-blind, parallel-group, multiple-dose trial was designed as
non-inferiority trial for efficacy of cebranopadol versus morphine PR. Planned
with 524 patients, finally 126 patients were treated for up to 7 weeks (low
accrual). The primary efficacy endpoint was the average amount of daily rescue
medication intake (morphine immediate release) over the last 2 weeks of
RESULTS: For the primary endpoint, non-inferiority of cebranopadol with and
superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95%CI]=-7.48
mg [-12.05, -2.92]; Per Protocol Set: ∆[95%CI]=-4.67 mg [-9.25, -0.10]). The vast
majority of patients (≥75%, either treatment) had clinically relevant pain
reduction, non-inferiority on this secondary endpoint was not shown. Mostly used
doses were ≤800 μg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of
patients on cebranopadol and 82.0% on morphine PR experienced treatment-emergent
CONCLUSIONS: Cebranopadol was effective, safe, and well tolerated in the dose
range tested (200 to 1,000 μg) in patients suffering from chronic moderate to
severe cancer-related pain and was superior to morphine PR on the primary
endpoint. This article is protected by copyright. All rights reserved.
2. Clin Pharmacokinet. 2018 Jan;57(1):31-50. doi: 10.1007/s40262-017-0545-1.
Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class
Kleideiter E(1), Piana C(2), Wang S(2), Nemeth R(3), Gautrois M(4).
(1)Data Sciences-Clinical Pharmacology, Grünenthal GmbH, Zieglerstrasse 6, 52078,
Aachen, Germany. firstname.lastname@example.org.
(2)Data Sciences-Pharmacometrics, Grünenthal GmbH, Aachen, Germany.
(3)Data Sciences-Biostatistics, Grünenthal GmbH, Aachen, Germany.
(4)Preclinical Drug Development-Pharmacokinetics, Grünenthal GmbH, Aachen,
Clin Pharmacokinet. 2018 Aug;57(8):1057-1058.
BACKGROUND AND OBJECTIVES: Cebranopadol is a novel first-in-class analgesic
acting as a nociceptin/orphanin FQ peptide and opioid peptide receptor agonist
with central analgesic activity. It is currently in clinical development for the
treatment of chronic pain conditions. This trial focuses on the clinical
pharmacokinetic (PK) properties of cebranopadol after oral single- and
METHODS: The basic PK properties of cebranopadol were assessed by means of
noncompartmental methods in six phase I clinical trials in healthy subjects and
patients. A population PK analysis included two further phase I and six phase II
RESULTS: After oral administration of the immediate-release (IR) formulation,
cebranopadol is characterized by a late time to reach maximum plasma
concentration [C max] (4-6 h), a long half-value duration [HVD] (14-15 h), and a
terminal phase half-life in the range of 62-96 h. After multiple once-daily
dosing in patients, an operational half-life (the dosing interval resulting in an
accumulation factor [AF] of 2) of 24 h was found to be the relevant factor to
describe the multiple-dose PKs of cebranopadol. The time to reach steady state
was approximately 2 weeks, the AF was approximately 2, and peak-trough
fluctuation (PTF) was low (70-80%). Dose proportionality at steady state was
shown for a broad dose range of cebranopadol 200-1600 µg. A two-compartment
disposition model with two lagged transition compartments and a first-order
elimination process best describes cebranopadol data in healthy subjects and
patients after single- and multiple-dose administration.
CONCLUSIONS: Cebranopadol formulated as an IR product can be used as a once-daily
formulation; it reaches C max after only 4-6 h, and has a long HVD and a low PTF.
Therefore, from a PK perspective, cebranopadol is an attractive treatment option
for patients with chronic pain.
3. J Clin Pharm Ther. 2017 Feb;42(1):8-17. doi: 10.1111/jcpt.12461. Epub 2016 Oct
Cebranopadol: novel dual opioid/NOP receptor agonist analgesic.
Raffa RB(1)(2), Burdge G(1), Gambrah J(1), Kinecki HE(1), Lin F(1), Lu B(1),
Nguyen JT(1), Phan V(1), Ruan A(1), Sesay MA(1), Watkins TN(1).
(1)Temple University School of Pharmacy, Philadelphia, PA, USA.
(2)University of Arizona College of Pharmacy, Tucson, AZ, USA.
WHAT IS KNOWN AND OBJECTIVE: Chronic pain presents a difficult clinical challenge
because of the limited efficacy, the limiting adverse-effect profile or the abuse
potential of current analgesic options. Cebranopadol is a novel new agent in
clinical trials that combines dual agonist action at opioid and
nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique,
centrally acting analgesic in several years. We here review the basic and
clinical pharmacology of cebranopadol.
METHODS: Published literature and Internet sources were searched to identify
information related to the basic science (pharmacology and medicinal chemistry)
and development (clinical trial) information on the mechanism of dual opioid and
NOP receptor pharmacologic action in general, and for cebranopadol in particular.
The identified sources were reviewed and the information synthesized.
RESULTS: The preclinical testing of cebranopadol has characterized it as a dual
opioid and NOP receptor agonist that displays antinociceptive and
antihyperalgesic action in a variety of acute and chronic pain models in animals.
Unlike most current traditional opioids, it is generally more potent against
neuropathic than nociceptive pain. Several phase 2 clinical trials have been
WHAT IS NEW AND CONCLUSION: Despite the medical need, a truly novel centrally
acting analgesic has not been developed in many years. Cebranopadol represents a
truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits
the results of phase 3 clinical trials.