A Phase 1, Randomized, 2-way Crossover, Food-effect Study of Ecopipam Pharmacokinetics After Administration of the To Be Marketed Tablet in Healthy Subjects

Standard food-effect study to identify the effect of food on ecopipam pharmacokinetics after administration of a to-be-marketed ecopipam tablet in healthy volunteers.

Start Date05 Nov 2024

Sponsor / Collaborator

Emalex Biosciences, Inc.Startup

NCT06194864 / CompletedPhase 1

A Phase 1, Sequential Drug Interaction Study to Evaluate the Effect of CYP3A4 and P-glycoprotein Inhibition by Itraconazole or Induction by Rifampicin on the Pharmacokinetics of Ecopipam and Its Metabolites in Healthy Subjects

This is a single center, 2-Part, Phase 1, open-label, fixed-sequence, drug-drug interaction study designed to compare the PK of ecopipam when administered alone and in combination with itraconazole (Part 1) or rifampicin (Part 2) in healthy subjects.

Start Date18 Jan 2024

Sponsor / Collaborator

Emalex Biosciences, Inc.Startup

[+2]

NCT06021522 / RecruitingPhase 3

A Multicenter, Open-Label, Study to Evaluate the Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder

The primary objective of this study is to evaluate the long-term safety and tolerability of ecopipam tablets in children (greater than or equal to [>=] 6 and less than [<] 12 years of age), adolescents (>=12 and <18 years of age), and adults (>=18 years of age) with Tourette's Syndrome (TS).

Start Date16 Aug 2023

Sponsor / Collaborator

Emalex Biosciences, Inc.Startup

100 Clinical Results associated with Ecopipam

100 Translational Medicine associated with Ecopipam

100 Patents (Medical) associated with Ecopipam

215

Literatures (Medical) associated with Ecopipam

29 Nov 2023·The Journal of neuroscience : the official journal of the Society for Neuroscience

The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice

Article

Author: Yan, Wenjun ; Wang, Qiongsi ; Chen, Kaijie ; Tian, Ruikang ; Huang, Furong ; Qu, Jia ; Zhou, Xiangtian ; Huang, Qin ; Xiong, Weiwei ; Wu, Honglin ; Shu, Ziheng ; Zhang, Chunlan ; Zhu, Yangfeifei

Dopamine is a key neurotransmitter in the signaling cascade controlling ocular refractive development, but the exact role and site of action of dopamine D1 receptors (D1Rs) involved in myopia remains unclear. Here, we determine whether retinal D1Rs exclusively mediate the effects of endogenous dopamine and systemically delivered D1R agonist or antagonist in the mouse form deprivation myopia (FDM) model. Male C57BL/6 mice subjected to unilateral FDM or unobstructed vision were divided into the following four groups: one noninjected and three groups that received intraperitoneal injections of a vehicle, D1R agonist SKF38393 (18 and 59 nmol/g), or D1R antagonist SCH39166 (0.1 and 1 nmol/g). The effects of these drugs on FDM were further assessed inDrd1-knock-out (Drd1-KO), retina-specific conditionalDrd1-KO (Drd1-CKO) mice, and corresponding wild-type littermates. In the visually unobstructed group, neither SKF38393 nor SCH39166 affected normal refractive development, whereas myopia development was attenuated by SKF38393 and enhanced by SCH39166 injections. InDrd1-KO orDrd1-CKO mice, however, these drugs had no effect on FDM development, suggesting that activation of retinal D1Rs is pertinent to myopia suppression by the D1R agonist. Interestingly, the development of myopia was unchanged by eitherDrd1-KO orDrd1-CKO, and neither SKF38393 nor SCH39166 injections, norDrd1-KO, affected the retinal or vitreal dopamine and the dopamine metabolite DOPAC levels. Effects on axial length were less marked than effects on refraction. Therefore, activation of D1Rs, specifically retinal D1Rs, inhibits myopia development in mice. These results also suggest that multiple dopamine D1R mechanisms play roles in emmetropization and myopia development.SIGNIFICANCE STATEMENTWhile dopamine is recognized as a “stop” signal that inhibits myopia development (myopization), the location of the dopamine D1 receptors (D1Rs) that mediate this action remains to be addressed. Answers to this key question are critical for understanding how dopaminergic systems regulate ocular growth and refraction. We report here the results of our study showing that D1Rs are essential for controlling ocular growth and myopia development in mice, and for identifying the retina as the site of action for dopaminergic control via D1Rs. These findings highlight the importance of intrinsic retinal dopaminergic mechanisms for the regulation of ocular growth and suggest specific avenues for exploring the retinal mechanisms involved in the dopaminergic control of emmetropization and myopization.

01 Apr 2023·Pharmacology research & perspectives

Ultra‐high‐field pharmacological functional MRI of dopamine D1 receptor‐related interventions in anesthetized rats

Article

Author: Kimura, Yuka ; Nishigori, Kantaro ; Yoshioka, Yoshichika ; Nakazawa, Shunsuke ; Mori, Yuki ; Ichihara, Junji

Abstract:

The dopamine D1 receptor (D1R) is associated with schizophrenia, Parkinson's disease, and attention deficit hyperactivity disorder. Although the receptor is considered a therapeutic target for these diseases, its neurophysiological function has not been fully elucidated. Pharmacological functional MRI (phfMRI) has been used to evaluate regional brain hemodynamic changes induced by neurovascular coupling resulting from pharmacological interventions, thus phfMRI studies can be used to help understand the neurophysiological function of specific receptors. Herein, the blood oxygenation level‐dependent (BOLD) signal changes associated with D1R action in anesthetized rats was investigated by using a preclinical ultra‐high‐field 11.7‐T MRI scanner. PhfMRI was performed before and after administration of the D1‐like receptor agonist (SKF82958), antagonist (SCH39166), or physiological saline subcutaneously. Compared to saline, the D1‐agonist induced a BOLD signal increase in the striatum, thalamus, prefrontal cortex, and cerebellum. At the same time, the D1‐antagonist reduced the BOLD signal in the striatum, thalamus, and cerebellum by evaluating temporal profiles. PhfMRI detected D1R‐related BOLD signal changes in the brain regions associated with high expression of D1R. We also measured the early expression of c‐fos at the mRNA level to evaluate the effects of SKF82958 and isoflurane anesthesia on neuronal activity. Regardless of the presence of isoflurane anesthesia, c‐fos expression level was increased in the region where positive BOLD responses were observed with administration of SKF82958. These findings demonstrated that phfMRI could be used to identify the effects of direct D1 blockade on physiological brain functions and also for neurophysiological assessment of dopamine receptor functions in living animals.

01 Feb 2023·Pediatrics

Ecopipam for Tourette Syndrome: A Randomized Trial

Article

Author: Dubow, Jordan S. ; Mahableshwarkar, Atul R. ; Cunniff, Timothy M. ; Gilbert, Donald L. ; Wanaski, Stephen P. ; Atkinson, Sarah D.

BACKGROUND AND OBJECTIVES:

All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome.

METHODS:

This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit.

RESULTS:

Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences −3.44, 95% confidence interval −6.09 to −0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events.

CONCLUSIONS:

Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.

News (Medical) associated with Ecopipam

24 Jul 2024

·www.fiercebiotech.com

Tourette's biotech Asarina to wind down after outreach to 200 companies fails to produce a partner

Asarina Pharma revealed in April 2023 that its Tourette syndrome therapy reduced tic severity at 12 weeks by 28%. After reaching out to more than 200 companies to partner a Tourette syndrome therapy that showed the ability to beat standard of care last year, Asarina Pharma has come up empty and will fold. The company asked shareholders to vote to liquidate in a notice posted Monday, the culmination of more than a year of effort to find a savior for the treatment called sepranolone. The Swedish company revealed in April 2023 that the therapy reduced tic severity at 12 weeks by 28% according to a common rating scale of disease severity called the Yale Global Tic Severity Scale (YGTSS), compared to 12.6% in patients who received standard of care. The phase 2a study also hit key secondary endpoints, including improving quality of life, and there were no systemic side effects observed. The open-label study randomized 28 patients to receive the experimental medicine or standard of care, with 17 receiving sepranolone. But those results were not enough to secure a partner, despite a grand effort from the Asarina team. In a proposal to liquidate issued July 18, the company said 200 parties had been contacted with 20 entities expressing interest in a potential in-licensing or acquisition deal. Several went as far as conducting due diligence on the clinical data. But none of those talks resulted in an offer. Asarina also explored a capital raise “but unfortunately has been forced to conclude that conditions for this are missing,” according to the notice. The company currently has equity of -635,000 Swedish kronor (-$59,000). “In light of the company's financial and commercial situation … the board of directors sees no alternative but to propose a winding up of the company's operations in an orderly manner, which can be done through a liquidation,” the notice explained. A meeting will be held in August to consider the plan to wrap up, with a liquidation date slated for Dec. 1. ”After more than 15 years of R&D development and more than 15 months of partnering activities, it is disappointing that we have not been able to find a new home for sepranolone. We still believe that the compound has the potential to be an effective drug for Tourette's syndrome and other neurological disorders,” said board Chairman Paul De Potocki in a statement. While drug development in Tourette syndrome has not seen a lot of action in recent years, at least one biotech is working on it. Emalex Biosciences published phase 2b data last year for a candidate called ecopipam showing a 30% reduction on the YGTSS. The company did not detail placebo results but said the 30% value represented a significant reduction in the total number of tics compared to placebo. Ecopipam also had a different safety profile, showing adverse events including headache in 15% of recipients, insomnia in 15%, fatigue in 8% and drowsiness in 8%. Emalex raised a massive $250 million in series D funds in 2022, which was to be used to fund a phase 3 test. That trial is now underway as of March 2023.

Phase 2Clinical ResultAcquisition

05 Oct 2023

·www.biospace.com

Emalex Biosciences Releases Results of 12-Month Open-Label Extension Study for Tourette Syndrome Candidate

Long-term safety data collected in pediatric patients treated with investigational drug ecopipam; durable treatment effect reported with no evidence of tachyphylaxis CHICAGO--(BUSINESS WIRE)-- An open-label extension study of 121 pediatric patients with Tourette syndrome evaluated the safety pro the investigational drug ecopipam for up to 12-months of treatment. No new safety concerns were identified based on an evaluation of adverse events, physical exams, vital signs, laboratory results and safety scales, according to Emalex Biosciences. A durable effect was also observed over the course of the study based on evaluation of the patients’ motor and vocal tics, which were assessed every three months. The findings were first presented at the International Congress of Parkinson’s Disease and Movement Disorder Society in Copenhagen and will be highlighted at the Child Neurology Society Annual Meeting this week in Vancouver. Patients in the open-label study previously completed a Phase 2b clinical trial involving more than 150 children and adolescents that found ecopipam significantly reduced the total number of motor and vocal tics compared to placebo, according to a study published in the journal Pediatrics. In this open-label study, ecopipam was generally well tolerated, with 33.1% (40/121) of patients reporting treatment-related adverse reactions (ARs). The most common ARs were anxiety (6.6%), insomnia (5.8%), and somnolence (5.8%). One patient experienced a serious adverse reaction (obsessive thoughts) and 11.6% (14/121) of patients discontinued the study due to adverse events. In addition, patients did not have observable evidence of excessive weight gain or metabolic side effects commonly reported with antipsychotic agents, which are often used to treat patients with Tourette syndrome. Ecopipam is a first-in-class dopamine-1 receptor antagonist. The antipsychotic agents currently approved to treat Tourette syndrome target the dopamine-2 receptor. Ecopipam is the lead candidate for Emalex Biosciences, a clinical-stage biopharmaceutical company founded by Paragon Biosciences. Emalex is currently conducting a Phase 3 clinical trial of ecopipam for the treatment of Tourette syndrome at more than 90 sites in North America and Europe. Tourette syndrome is a chronic, childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. The condition is associated with both increased mortality and significant morbidity. In the majority of individuals, Tourette syndrome substantially impacts day-to-day physical and social function. “The fact that most patients who completed the Phase 2b study asked to participate in the open-label extension points to the unmet medical needs for people with Tourette syndrome. The 12-month data supports the continued development of ecopipam as a first-in-class novel therapy for children and adolescents with Tourette syndrome,” said Emalex Biosciences Chief Medical Officer Frederick Munschauer, MD. About Ecopipam Emalex’s first-in-class development candidate ecopipam, a novel investigational compound that is being studied as a potential treatment for certain central nervous system disorders, blocks the actions of the neurotransmitter dopamine at the D1 receptor. Dopamine is a neurotransmitter in the central nervous system, and its receptors have been classified into two “families” based on their genetic structure: “D1” (including subtypes D1 and D5) and “D2” (including subtypes D2, D3, and D4). D1 receptor super-sensitivity may be a mechanism for the repetitive and compulsive behaviors associated with Tourette syndrome. Currently approved therapies for the treatment of Tourette syndrome act at D2 receptors. Ecopipam has been shown to be generally well tolerated in clinical trials conducted to date and has received Orphan Drug and Fast Track designation from the FDA for the treatment of patients with Tourette syndrome. Adverse events affecting primarily the central nervous system have been reported in clinical trials conducted to date, including headache, fatigue, somnolence, insomnia, restlessness, anxiety, depression and rarely, suicidal ideation. About Emalex Biosciences Emalex Biosciences was created by Paragon Biosciences to develop new treatments for central nervous system disorders. Emalex is in late-stage development of a new class of drug targeting the D1 receptor for patients with Tourette syndrome and other conditions that have limited treatment options. Visit to learn more. About Paragon Biosciences, LLC Paragon Biosciences is a global life science leader that creates, builds and funds innovative biology-based companies in three key areas: cell and gene therapy, biology engineering and advanced biotechnology. Our portfolio companies use biology to accelerate scientific breakthroughs that solve some of society’s most challenging problems. Learn more at .

Phase 2Orphan DrugFast TrackClinical ResultPhase 3

01 Mar 2023

·www.prnewswire.com

Emalex Biosciences Announces First Patient Dosed in Phase 3 Trial of Ecopipam for Tourette Syndrome

Enrolled patients will receive medication for up to 24 weeks; 90 sites planned for North America and Europe CHICAGO, March 1, 2023 /PRNewswire/ -- Emalex Biosciences announced that the first patient was dosed in its Phase 3 clinical trial evaluating ecopipam for the treatment of Tourette Syndrome. Continue Reading Participants in the trial receive ecopipam for 12 weeks in the open-label phase of the study. Those with at least a 25% reduction in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at both week 8 and 12 will be randomized to continue on ecopipam or placebo in the double-blind phase of the study until they relapse, up to an additional 12 weeks. Efficacy will be assessed as the difference in time-to-relapse between groups. Participants in the trial receive ecopipam for 12 weeks in the open-label phase of the study. Tweet this "Tourette Syndrome is a serious condition for which there is significant unmet need," said Amanda Talty, Tourette Association of America president and CEO. "Currently, the two classes of medicines commonly used to treat Tourette can have a number of concerning side effects. We are happy to see the progress of additional studies being conducted to test new treatment alternatives for our community." Emalex closed an upsized and oversubscribed $250 million Series D round led by Bain Capital Life Sciences in November to fund the Phase 3 trial and potential commercialization of ecopipam. The trial is expected to enroll more than 200 patients across 90 sites in North America and Europe. Ecopipam is a first-in-class dopamine-1 receptor antagonist. The antipsychotic agents currently approved to treat Tourette syndrome target the dopamine-2 receptor and are associated with serious side effects. Patients enrolled in the Phase 2b D1AMOND study did not have observable evidence of adverse movements, excessive weight gain, or the metabolic side effects commonly reported with antipsychotic agents. The most frequent ecopipam-related adverse events in the study were headache (9.2%), fatigue (6.6%), somnolence (6.6%), insomnia (5.3%), and restlessness (5.3%). Tourette Syndrome is a chronic, childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. The condition is associated with both increased mortality and significant morbidity. In the majority of individuals, Tourette Syndrome substantially impacts day-to-day physical and social function. Principal investigator Donald Gilbert, MD, a movement disorders specialist at the Cincinnati Children's Hospital, noted patients' tics often cause pain and injury in addition to social stigma and emotional distress. "My patients have an urgent need for safer and more effective treatments. Tourette interferes with daily activities and commonly has negative impacts on mental and emotional health. For children and teens, Tourette can affect school performance and social development, which has lifelong consequences," Dr. Gilbert said. About Ecopipam Emalex's first-in-class development candidate, ecopipam, is a novel investigational compound that is being studied as a potential treatment for certain central nervous system disorders. Ecopipam blocks the actions of the neurotransmitter dopamine at the D1 receptor. Dopamine is a neurotransmitter in the central nervous system, and its receptors have been classified into two "families" based on their genetic structure: "D1" (including subtypes D1 and D5) and "D2" (including subtypes D2, D3, and D4). D1 receptor super-sensitivity may be a mechanism for the repetitive and compulsive behaviors associated with Tourette syndrome. Currently approved therapies for the treatment of Tourette syndrome act at D2 receptors. Ecopipam has been shown to be generally well tolerated in clinical trials conducted to date and has received Orphan Drug and Fast Track designation from the FDA. Adverse events affecting primarily the central nervous system have been reported in clinical trials conducted to date include headache, fatigue, somnolence, insomnia, restlessness, anxiety, depression and rarely, suicidal ideation. Further information can be found on clinicaltrials.gov. About Emalex Biosciences Emalex Biosciences was created by Paragon Biosciences to develop new treatments for central nervous system disorders. Emalex is in late-stage development of a new class of drug targeting the D1 receptor for patients with Tourette syndrome and other conditions that have limited treatment options. Visit to learn more About Paragon Biosciences Paragon Biosciences is a global life science leader that creates, builds and funds innovative biology-based companies in three key areas: cell and gene therapy, biology engineering and advanced biotechnology. Our portfolio companies use biology to accelerate scientific breakthroughs that solve some of society's most challenging problems. Learn more at . Media Contact: Sheridan Chaney 312.847.1323 [email protected] SOURCE Emalex Biosciences

Phase 3Orphan DrugPhase 2Fast Track

100 Deals associated with Ecopipam

External Link

KEGG	Wiki	ATC	Drug Bank
D03937	Ecopipam	-	DB12273

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Tourette Syndrome	Phase 3	US	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	BG	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	CA	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	DK	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	FR	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	DE	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	HU	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	IT	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	PL	Emalex Biosciences, Inc.Startup	31 Jan 2023
Tourette Syndrome	Phase 3	RO	Emalex Biosciences, Inc.Startup	31 Jan 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04114539 (CTgov)	Phase 2	Tourette Syndrome	124	Ecopipam HCI	flfubfabqu(btbonrucyl) = bxytjxzgea gervaxattc (izbwemvhis, ytigszebmn - owwrcjfsdp) View more	-	01 Dec 2023
Corporate Publications Manual	Phase 2	Tourette Syndrome	-	Ecopipam	fbwuimvlml(teullmdzfh) = jyvcsiqank hhgegrjsna (pimadmltfa ) View more	Positive	05 Oct 2023
NCT04007991 (D1AMOND, CTgov)	Phase 2	Tourette Syndrome	153	Ecopipam (Ecopipam HCI 2 mg/kg/Day)	vncqxjpvlp(sfsipctggd) = oqwuppucez ulxetwkibo (dbvijuwkgb, orwzpxrjwn - iwwjuepmne) View more	-	04 Oct 2023
NCT04007991 (D1AMOND, CTgov)	Phase 2	Tourette Syndrome	153	Placebo (Placebo)	vncqxjpvlp(sfsipctggd) = pjsgfpybak ulxetwkibo (dbvijuwkgb, qxaehhwqkg - znqxnnaukh) View more	-	04 Oct 2023
Phase 2b Study of Ecopipam (MDS2022)	Phase 2	Tourette Syndrome	153	Ecopipam	poxtzmlhxn(atkeuhxfko): LS mean [SE] difference = -3.4 (95% CI, -6.1 to -0.8), P-Value = 0.011 View more	Positive	15 Sep 2022
Phase 2b Study of Ecopipam (MDS2022)	Phase 2	Tourette Syndrome	153	Placebo		Positive	15 Sep 2022
MDS2021	Phase 2	Tourette Syndrome	26	Ecopipam	yifcextrbx(oyhtfxukqr) = ubolrrwysg cqkdyzbdkm (zorzzzkocz )	Positive	17 Sep 2021
MDS2019	Not Applicable	Restless Legs Syndrome	10	Ecopipam	(idbteeqxus) = Tolerability was very good mtkgivwmwq (cimolymcqp ) View more	Positive	22 Sep 2019
MDS2019	Not Applicable	Restless Legs Syndrome	10	Placebo		Positive	22 Sep 2019
NCT01065558 (Pubmed \| Mol Genet Metab) Manual	Phase 1	Lesch-Nyhan Syndrome	5	ecopipam	spumzkcaeh(kuilnkrpbq) = sedation being the most common dose-limiting event cmqxeupuzk (mxafziagzj )	Positive	01 Apr 2016
NCT01751802 (CTgov)	Phase 3	Lesch-Nyhan Syndrome \| Self-Injurious Behavior	9	Ecopipam (Ecopipam)	zrsjyzbswe(ynnrweocid) = wlbziygiuc uzokajhzkf (uhkkyinbhr, hfvqyyruyj - znpagknegn) View more	-	08 Oct 2015
NCT01751802 (CTgov)	Phase 3	Lesch-Nyhan Syndrome \| Self-Injurious Behavior	9	Placebo (Placebo)	zrsjyzbswe(ynnrweocid) = avhcjmuege uzokajhzkf (uhkkyinbhr, hpaakqeawn - rhrvngsmkl) View more	-	08 Oct 2015
NCT01244633 (CTgov)	Phase 1/2	Tourette Syndrome	18	Ecopipam	vhwoapahrd(rnsokinzts) = mllusbyosi qhaiclyhar (xzjrmegbbm, dxktjxyfen - pafnlsuhse) View more	-	29 Sep 2015
NCT02909088 (Pubmed \| Clin Neuropharmacol)	Phase 2/3	Tourette Syndrome	18	Ecopipam 50 mg	jbiforcxvb(nnwlztwema) = 22% ymjxntkpzd (lbsyeovtyp ) View more	-	01 Jan 2014

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