Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms

Figures & data

Figure 1. Chemical structure of Elinzanetant (NT-814) [44].

Table 1. Overview about clinical studies on Elinzanetant.

Author, year	Pawsey et al., 2021	Trower et al., 2020	Simon et al., 2023
Reference	[44]	[45]	[46]
Study name	–	RELENT-1	SWITCH-1
Clinical trial registry number	ISRCTN11913515	NCT02865538	NCT03596762
Clinical trial phase	I	IIb	IIb
Inclusion criteria	Premenopausal women	Postmenopausal women
	18–45 years	40–65 years
	Healthy, ovulatory women	7–20 moderate to severe hot flashes/day	≥7 moderate hot flashes/day
Number of randomized subjects	33	76	199
Route of administration	Oral	Oral	Oral
Elinzanetant doses	Placebo	Placebo	Placebo
	40 mg/80 mg/ 120 mg per day	50 mg/100 mg/ 150 mg/300 mG per day	40 mg/80 mg/ 120 mg/160 mg per day
Treatment duration	1 menstrual cycle	14 days	12 weeks
Primary endpoint	FSH, LH, estradiol serum levels	Safety	Frequency and severity of hot flashes
Secondary endpoint	–	Number and severity of hot flashes	Frequency and severity of hot flashes, sleep quality, ISI, PSQI, and MenQoL-I scores

Abbreviations used: ISI, Insomnia Severity Index questionnaire; PSQI, Pittsburgh Sleep Quality Index, MenQol-I, Menopause-specific Quality-of-Life questionnaire intervention.

Table 2. Overview of the most common treatment-specific adverse events of Elinzanetant in the RELENT-1 [45] and SWITCH-1 [46] studies.

	RELENT-1 [45]				SWITCH-1 [46]
Adverse event	50 mg	100 mg	150 mg	300 mg	40 mg	80 mg	120 mg	160 mg	Pooled incidence
N	15	15	15	13	31	17	52	52	210
Somnolence	5 (33.3)	2 (13.3)	5 (33.3)	9 (69.2)	0	2 (11.8)	0	5 (9.6)	28 (13.3)
Headache	0	5 (33.3)	1 (6.7)	6 (46.2)	3 (9.7)	2 (11.8)	6 (11.5)	4 (7.7)	27 (12.9)
Diarrhea	1 (6.7)	0	1 (6.7)	3 (23.1)	2 (6.5)	2 (11.8)	3 (5.8)	3 (5.8)	15 (7.1)

Data are provided as n (%).

Ratti E, Bettica P, Alexander R, et al. Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. J Psychopharmacol. 2013;27(5):424–434. doi: 10.1177/0269881113480990

 PubMed Web of Science ®Google Scholar

Ratti E, Carpenter DJ, Zamuner S, et al. Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia. Sleep. 2013;36(12):1823–1830. doi: 10.5665/sleep.3208

 PubMed Web of Science ®Google Scholar

Ridler K, Gunn RN, Searle GE, et al. Characterising the plasma-target occupancy relationship of the neurokinin antagonist GSK1144814 with PET. J Psychopharmacol. 2014;28(3):244–253. doi: 10.1177/0269881113517953

 PubMed Web of Science ®Google Scholar