Delving into the Latest Updates on GSK-2881078 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

AR

Mechanism

AR modulators(Androgen Receptor modulators)

Therapeutic Areas

Nervous System DiseasesRespiratory DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

CachexiaMuscle WeaknessPulmonary Disease, Chronic Obstructive

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H13F3N2O2S

InChIKeySKDVMPZQJMZEAC-SECBINFHSA-N

CAS Registry1539314-06-1

A Randomized, Double-blind (Sponsor Unblind), Placebo-controlled, Multi-centred Phase IIa Study to Evaluate the Safety and Efficacy of 13 Weeks of Once Daily Oral Dosing of the Selective Androgen Receptor Modulator (SARM) GSK2881078 in Older Men and Post Menopausal Women With COPD and Muscle Weakness, Participating in Home Exercise

Impaired physical function and muscle dysfunction are a major consequence of COPD, which may be associated with increased mortality, poor quality of life and increased health care use. This is a randomized, placebo-controlled, double-blind, parallel group study to evaluate the safety and tolerability of GSK2881078, an SARM over 13 weeks of dosing in older male subjects and post-menopausal female subjects with COPD and muscle weakness. This study will also assess the effect of GSK2881078 on physical strength and function after 13 weeks of treatment. Approximately 100 subjects with COPD and muscle weakness will be randomized into two cohorts of 50 male subjects and 50 female subjects. Within each cohort, subjects will be randomized to receive GSK2881078 or placebo in a ratio of 1:1. All subjects will participate in a standardized home exercise program, which will consist of daily walking, along with several resistance or weight-bearing exercises, such as bicep curls, upright rows, step ups and a sit-to-stand maneuver. The study will consist of a screening/Baseline period of up to 30 days, a 13-week treatment period and a post-treatment follow-up period of 6 weeks.

Start Date28 Feb 2018

Sponsor / Collaborator

GSK Plc

[+1]

NCT02567773 / CompletedPhase 1

A Randomized Double-blind (Sponsor Unblind) Placebo Controlled Study in Healthy Subjects to Evaluate: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Repeat Doses of GSK2881078, the Selective Androgen Receptor Modulator With an Open Label Dosing Arm to Evaluate the Effect of CYP3A4 Inhibition on Pharmacokinetics of GSK2881078

GSK2881078 is a selective androgen receptor modulator (SARM) that is being evaluated for effects on muscle growth and strength in subjects with muscle wasting to improve their physical function. Part A of this study will evaluate the safety, efficacy and pharmacokinetics of GSK2881078 in healthy, older men and post-menopausal women who will take daily dosing for 28 days and be followed for a total of 70 days. Part B of this study will characterize the effect of Cytochrome P450 3A4 (CYP3A4) inhibition on the GSK2881078 pharmacokinetics. Part B will only be conducted if safe and efficacious dose is identified in Part A. Part A will include healthy older males and post-menopausal females; and randomize approximately 60 subjects (about 15 per cohort [4 cohorts]) to complete approximately 48 (about 12 per cohort). Part B will enroll one cohort of approximately 15 healthy male subjects to complete approximately 12. The study duration will be approximately 115 days for Part A and 122 days for Part B.

Start Date01 Sep 2015

Sponsor / Collaborator

GSK Plc

NCT02045940 / CompletedPhase 1

A Randomized Double Blinded (Sponsor Unblind), Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM) in Single and Repeat Doses in Healthy Male Subjects

This study is the first administration of GSK2881078 to humans. The intention of this study is to provide sufficient confidence in the safety of the molecule to inform progression to further repeat dose and proof of concept studies. This study will include approximately 52 subjects and consist of 2 parts. Part A will consist of two cohorts of 8 subjects to assess the safety, tolerability, and pharmacokinetic (PK) of ascending single oral doses of GSK2881078. Cohorts 1 and 2 will include healthy male subjects. Part B (Cohorts 3, 4 and 5) will include three cohorts of 12 healthy male subjects to examine the safety, tolerability, PK, and pharmacodynamic (PD) of repeated doses of GSK2881078 over 14 days. The total duration of the study including screening and follow-up, is not expected to exceed 70 days.

Start Date20 Jan 2014

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-2881078

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100 Translational Medicine associated with GSK-2881078

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100 Patents (Medical) associated with GSK-2881078

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12

Literatures (Medical) associated with GSK-2881078

01 Jul 2023·Drug testing and analysis

In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control.

Article

Author: Subhahar, Michael Benedict ; Graiban, Fatma Mohammed ; Caveney, Marina Rodriguez ; Karatt, Tajudheen K ; Philip, Moses ; Laya, Saraswathy ; Kal, Abdul Khader Karakka ; Sathiq, M Anwar ; Muhammed Ajeebsanu, M P

Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid chromatography-high-resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of five (M1-M5) in vivo metabolites and six (M1-M6) in vitro metabolites were detected under experimental conditions. Phase I metabolites mainly result from hydroxylation. Methoxylated and side-chain dissociated metabolites were also detected. Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of nonsteroidal SARM GSK2881078 and reveal its illicit use in competitive sports.

01 Mar 2023·Thorax

Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial

Article

Author: Russell, Alan J ; Mohan, Divya ; Rossiter, Harry ; Thomas, Sebin ; Beerahee, Misba ; Watz, Henrik ; Evans, Rachael A ; Millns, Helen ; Kumar, Subramanya ; Tabberer, Maggie ; Fogarty, Charles ; Polkey, Michael I ; Man, William ; Neil, David ; Akinseye, Chika ; Holland, Marie Claire ; Tal-Singer, Ruth

BackgroundSelective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength in patients with chronic obstructive pulmonary disease (COPD) and impaired physical function.Methods47 postmenopausal women and 50 men with COPD (forced expiratory volume in 1 s 30%–65% predicted; short physical performance battery score: 3–11) were enrolled into a randomised double-blind, placebo control trial. Patients were randomised 1:1 to once daily placebo or oral GSK2881078 (females: 1.0 mg; males: 2.0 mg) for 13 weeks with a concurrent home-exercise programme, involving strength training and physical activity. Primary endpoints were change from baseline in leg strength at 90 days (one-repetition maximum; absolute (kg) and relative (% change)) and multiple safety outcomes. Secondary endpoints included lean body mass, physical function and patient-reported outcomes.ResultsGSK2881078 increased leg strength in men. The difference in adjusted mean change from baseline and adjusted mean percentage change from baseline between treatment and placebo were: for women, 8.0 kg (90% CI −2.5 to 18.4) and 5.2% (90% CI −4.7 to 15.0), respectively; for men, 11.8 kg (90% CI −0.5 to 24.0) and 7.0% (90% CI 0.5 to 13.6), respectively. Lean body mass increased, but no changes in patient-reported outcomes were observed. Reversible reductions in high-density lipoprotein-cholesterol and transient elevations in hepatic transaminases were the main treatment-related safety findings.ConclusionsGSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone.Trial registration numberNCT03359473.

01 Feb 2022·Drug Testing and AnalysisQ2 · MEDICINE

Identification of equine in vitro metabolites of seven non‐steroidal selective androgen receptor modulators for doping control purposes

Q2 · MEDICINE

Article

Author: Taylor, Polly ; Cutler, Charlotte ; Viljanto, Marjaana ; Hincks, Pamela ; Van Eenoo, Peter ; Biddle, Simon

AbstractSelective androgen receptor modulators, SARMs, are a large class of compounds developed to provide therapeutic anabolic effects with minimal androgenic side effects. A wide range of these compounds are available to purchase online and thus provide the potential for abuse in sports. Knowledge of the metabolism of these compounds is essential to aid their detection in doping control samples. In vitro models allow a quick, cost‐effective response where administration studies are yet to be carried out. In this study, the equine phase I metabolism of the non‐steroidal SARMs GSK2881078, LGD‐2226, LGD‐3303, PF‐06260414, ACP‐105, RAD‐140 and S‐23 was investigated using equine liver microsomes. Liquid chromatography coupled to a QExactive Orbitrap mass spectrometer allowed identification of metabolites with high resolution and mass accuracy. Three metabolites were identified for both GSK2881078 and LGD‐2226, four for LGD‐3303 and RAD‐140, five for PF‐06260414, twelve for ACP‐105 and ten for S‐23. The equine metabolism of GSK‐2881078, LGD‐2226, LGD‐3303 and PF‐06260414 is reported for the first time. Although the equine metabolism of ACP‐105, RAD‐140 and S‐23 has previously been reported, the results obtained in this study have been compared with published data.

100 Deals associated with GSK-2881078

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cachexia	Phase 2	GB	GSK Plc	28 Feb 2018
Cachexia	Phase 2	DE	GSK Plc	28 Feb 2018
Cachexia	Phase 2	US	GSK Plc	28 Feb 2018
Muscle Weakness	Phase 2	US	GSK Plc	28 Feb 2018
Muscle Weakness	Phase 2	GB	GSK Plc	28 Feb 2018
Muscle Weakness	Phase 2	DE	GSK Plc	28 Feb 2018
Pulmonary Disease, Chronic Obstructive	Phase 2	DE	GSK Plc	28 Feb 2018
Pulmonary Disease, Chronic Obstructive	Phase 2	US	GSK Plc	28 Feb 2018
Pulmonary Disease, Chronic Obstructive	Phase 2	GB	GSK Plc	28 Feb 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03359473 (Pubmed)	Phase 2	Pulmonary Disease, Chronic Obstructive	97	GSK2881078	gzzahvakxe(wzbaukkczi) = bbxjwklenk pfmokklrql (htvecogmoc, -2.5 to 18.4)	Positive	25 Oct 2022
NCT03359473 (GSK Stage 1: 206869; Stage 2: 200182, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive \| Cachexia \| Muscle Weakness	97	Placebo (Placebo- Female Participants)	lxkrjdhgkz(tpveybngqr) = gtteqciesz qoawaagwvk (wldtymnoij, fkwlocsrvs - dsitnczgbt) View more	-	15 Jul 2020
				GSK2881078 (GSK2881078 1.0 mg- Female Participants)	lxkrjdhgkz(tpveybngqr) = eymjpnmazk qoawaagwvk (wldtymnoij, qgcyrplwcs - kxgtowcrwv) View more
NCT02045940 (Pubmed \| Br J Clin Pharmacol) Manual	Phase 1	-	99	GSK2881078	(wrfrglsuij): differences = -0.518 (95% CI, -0.703 to -0.334) View more	Positive	01 Oct 2017
				Placebo