Clinical trial NCT03463044: Safety, Tolerability and Pharmacokinetic Profiles of MOTREM (LR12) in Healthy Male Subjects
Official title: A Phase I, Randomised, Placebo Controlled Study to Assess the Safety, Tolerability and Pharmacokinetic Profiles of Ascending, Single, Intravenous Doses of MOTREM (LR12) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Inotrem
Sponsor class: INDUSTRY
Collaborators: name: Richmond Pharmacology Limited
First posted: 2018-03-13
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This was a single center, randomized, placebo-controlled study with a sequential i.v. dose escalation cohorts design, to assess safety, tolerability and pharmacokinetics of MOTREM (nangibotide) in healthy volunteers

Detailed description: This was a dose escalation study in healthy volunteers to evaluate the safety and pharmacokinetics of nangibotide in humans

Eligibility criteria: Inclusion Criteria:

* healthy male
* ≥18 to ≤45 years old
* Body mass index (BMI) between 18-30 kg/m² inclusive
* Written informed consent to participate.

Main Exclusion Criteria:

* Any clinically relevant acute or chronic diseases
* Any history of drug or alcohol abuse
* Any History of clinical significant disease as determined by medical history, physical examination or other evaluations.

Primary outcomes:
measure: Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events
timeFrame: 30-44 days
Secondary outcomes:
measure: Pharmacokinetics (Maximum Plasma Concentration)
timeFrame: Maximum Plasma Concentration (Cmax) was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cmax is determined over a period of time starting from predose to 10h after start of the loading dose.
measure: Statistical Analysis of LR12 PK Parameters: Steady State Concentration During the Maintenance Infusion (Cavg30-465)
timeFrame: Cavg30-465 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cavg30-465 is determined over a period of time starting from predose to 10h after start of the loading dose.
measure: Statistical Analysis of LR12 PK Parameters: t1/2
timeFrame: t1/2 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t1/2 is determined over a period of time starting from 7 h and 45 min to 10h after start of the loading dose (decaying period).
measure: Statistical Analysis of LR12 PK Parameters: AUC0-t
timeFrame: AUC0-t was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-t is determined over a period of time starting time zero (predose) to the time of last observed concentration (t).
measure: Statistical Analysis of LR12 PK Parameters: AUC0-∞
timeFrame: AUC0-∞ was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-∞ is determined over a period of time starting time zero (predose) to infinity (cf. extrapolation formula in the above section).
measure: Statistical Analysis of LR12 PK Parameters: CL
timeFrame: CL was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min (465 min). CL is calculated based on the perfusion rate (ng/kg/h) and the concentration at the end of perfusion (7h45min = 465min).
measure: Statistical Analysis of LR12 PK Parameters: Volume of Distribution (V)
timeFrame: V was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. V is derived from both CL and ke which are calculated from the LR12 concentration time curve from predose to 10h after loading dose start.
measure: Statistical Analysis of LR12 PK Parameters: Tmax
timeFrame: tmax was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. tmax is determined over a period of time starting from predose to 10h after start of the loading dose.
measure: Statistical Analysis of LR12 PK Parameters: t Last
timeFrame: t last was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t last is determined as the time of last observed concentration which can go up to 10h after loading dose start.
Other outcomes:
Locations:
city: Croydon
country: United Kingdom
facility: Richmond Pharmacology Ltd.
Study officials:
affiliation: Inotrem
name: Valérie Cuvier
role: STUDY_DIRECTOR
References:
citation: Cuvier V, Lorch U, Witte S, Olivier A, Gibot S, Delor I, Garaud JJ, Derive M, Salcedo-Magguilli M. A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition. Br J Clin Pharmacol. 2018 Oct;84(10):2270-2279. doi: 10.1111/bcp.13668. Epub 2018 Jul 20.