L-type calcium channel blockers(Voltage-gated L-type calcium channel blockers), T-type calcium channel blockers(Voltage-gated T-type calcium channel blockers)

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Essential Hypertension

Originator Organization

Actelion Pharmaceuticals Ltd.

Active Organization-

Inactive Organization

Idorsia Pharmaceuticals Ltd.

Actelion Pharmaceuticals Ltd.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC33H43N3O4

InChIKeyPEBSFLONQDNKQK-PHLCOOFXSA-N

CAS Registry1075744-31-8

Clinical Trials associated with ACT-280778

NCT01264692

/ CompletedPhase 2

A Multi-center, Double-blind, Randomized, Placebo- and Active-controlled, Parallel-group, Proof-of-concept Study to Evaluate the Efficacy, Safety, and Tolerability of 10 mg of ACT-280778 in Patients With Mild to Moderate Essential Hypertension

The purpose of this study is to demonstrate the antihypertensive efficacy of once daily oral administration of ACT 280778 on DBP compared to placebo after 28 days.

Start Date01 Feb 2011

Sponsor / Collaborator

Idorsia Pharmaceuticals Ltd.

100 Clinical Results associated with ACT-280778

100 Translational Medicine associated with ACT-280778

100 Patents (Medical) associated with ACT-280778

Literatures (Medical) associated with ACT-280778

01 Apr 2015·Journal of Human HypertensionQ4 · MEDICINE

Efficacy and safety of the dual L- and T-type calcium channel blocker, ACT-280778: a proof-of-concept study in patients with mild-to-moderate essential hypertension

Q4 · MEDICINE

Article

Author: Otasevic, P ; Kracker, H ; Klainman, E ; Mueller, M S ; Zimlichman, R ; Dingemanse, J ; Shakeri-Nejad, K ; Putnikovic, B

ACT-280778 is an oral, non-dihydropyridine, dual L-/T-type calcium channel blocker. This phase 2a, double-blind, randomized, placebo- and active-controlled study investigated the efficacy and safety of 10 mg ACT-280778. Patients with mild-to-moderate essential hypertension received once-daily placebo (n=53), ACT-280778 10 mg (n=52) or amlodipine 10 mg (n=54) for 4 weeks. The primary end point was the change from baseline to week 4 in placebo-adjusted mean trough sitting diastolic blood pressure (SiDBP) with ACT-280778. Tolerability was assessed by recording treatment-emergent adverse events (TEAEs). Baseline clinical characteristics were similar across groups. No significant difference was observed at week 4 in mean trough SiDBP between placebo (-9.9 (95% confidence limit (CL) -12.7, -7.0) mm Hg) and ACT-280778 (-9.5 (-12.4, -6.5) mm Hg; P=0.86); amlodipine reduced mean trough SiDBP by -16.8 (-19.0, -14.5) mm Hg, confirming assay validity. Change in mean PR interval at week 4 (pre-dose) differed between placebo (-1.0 (95% CL -4.4, 2.3) ms) and ACT-280778 (6.5 (3.5, 9.6) ms); amlodipine did not increase PR interval (1.1 (-1.6, 3.9) ms).Treatment-emergent adverse events (TEAE) frequency was 32.1% (placebo), 32.7% (ACT-280778) and 33.3% (amlodipine). The most common TEAEs were headache, peripheral edema, hypertension and second-degree atrioventricular block. ACT-280778 (10 mg) did not lower blood pressure in mild-to-moderate hypertension.

19 Dec 2014·Organic Process Research & Development

Diastereospecific Enolate Addition and Atom-Efficient Benzimidazole Synthesis for the Production of L/T Calcium Channel Blocker ACT-280778

Author: Funel, Jacques-Alexis ; Struijk, Martin ; Seidel, Thomas ; Litjens, Remy ; Abele, Stefan ; Guggisberg, Yves ; Brodbeck, Stephan

A scalable access to I (ACT-280778), a potent L/T calcium channel blocker, has been developed.The synthesis, amenable to kilogram manufacturing, comprises 10 chem. steps from enantiomerically pure 5-phenylbicyclo[2.2.2]-oct-5-en-2-one and 1,4-dimethoxybenzene with a longest linear sequence of 7 steps.Key to the success of this fit-for-purpose approach are a robust and atom-efficient access to benzimidazole II, the substrate-controlled diastereoselective enolate addition toward carboxylic acid III that was isolated by simple crystallization with high dr (>99:1), the convenient selective N-deacylation of intermediate IV, and the identification of a suitable solid form of I as the bis-maleate salt (1·2 C₄H₄O₄).As an illustration of the robustness of this process, 14 kg of drug substance, suitable for human use, was produced with an overall yield of 38% over the longest linear sequence (7 steps).

01 Feb 2014·Journal of Cardiovascular PharmacologyQ4 · MEDICINE

Early Clinical Studies in Healthy Male Subjects Using Adaptive Designs

Q4 · MEDICINE

Article

Author: Gutierrez, Marcelo M. ; Sanderson, Brian ; Mueller, Markus S. ; Dingemanse, Jasper ; Krause, Andreas ; Taeubel, Joerg ; Shakeri-Nejad, Kasra

ACT-280778 is a novel nondihydropyridine dual L/T-type calcium channel blocker. Two clinical studies (AC-067-101 and AC-067-102) were conducted to characterize its safety, tolerability, and pharmacokinetics in healthy male subjects after oral administration of single and multiple doses. Both trials were single-center, randomized, double-blind, placebo-controlled, adaptive design, ascending-dose studies, in which ACT-280778 was administrated as single doses of 2, 5, 15, or 40 mg, or as once-daily doses of 5 or 15 mg for 7 days. Single and multiple doses up to and including 15 mg were well tolerated, and no serious or severe adverse event was reported in either study. A single dose of 40 mg was associated with abnormal electrocardiogram findings resulting in the discontinuation of further treatment at this dose or higher doses. ACT-280778 was rapidly absorbed, and larger than dose-proportional increases of the maximum plasma concentration and area under the plasma concentration-time curve were observed. Food intake delayed the time to maximum plasma concentration and doubled exposure. Urinary excretion of unchanged ACT-280778 was negligible, and accumulation at steady state was modest. Overall, pharmacokinetic and tolerability profiles of ACT-280778 observed in these 2 studies warranted further evaluation of ACT-280778 in a proof-of-concept study in patients with hypertension.

100 Deals associated with ACT-280778

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Essential Hypertension	Phase 2	Israel	Actelion Pharmaceuticals Ltd.	-
Essential Hypertension	Phase 2	Israel	Actelion Pharmaceuticals Ltd.	-
Essential Hypertension	Phase 2	Serbia	Actelion Pharmaceuticals Ltd.	-
Essential Hypertension	Phase 2	Serbia	Actelion Pharmaceuticals Ltd.	-

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