Posts Tagged ‘Contract Research Organization CRO’

Questioning QT Interval Measurements? Look at the Anesthetic: Part 2

Posted by CorDynamics on March 16th, 2015

QT Questions Look at Anesthetic

CorDynamics will be presenting a poster at the upcoming 2015 Society of Toxicology meeting in San Diego entitled: The Differential Effect of Nembutal and Ketamine/Xylazine Anesthetic on Dofetilide-Induced QT Interval Prolongation. 

The objective was to advance upon our previous findings presented at SOT last year. (Read Part I: When Questioning QT Interval Measurements: Look at the Anesthetic.) This model examines the effects of dofetilide, an IKr antagonist known to prolong QT interval, on guinea pigs anesthetized with either Nembutal or ketamine/xylazine.

The anesthetized guinea pig is a widely used model for early screening of drug-candidate effects on cardiovascular function. This species also continues to gain traction for use in conscious telemetry screening.

In this study, we found that administration of dofetilide to either Nembutal or ketamine/xylazine anesthetized guinea pigs significantly increased QTcB interval at all doses tested compared to time-matched vehicle control. QTcB interval increased up to 22% in the Nembutal group, yet only reached 12% in the ketamine/xylazine group even though the dose was increased 5-fold in the latter cohort. There were no effects on mean arterial pressure, heart rate, or other ECG parameters in either group.

View Poster

Our data demonstrate that sodium pentobarbital anesthetized guinea pigs are more sensitive to QTc interval prolongation than ketamine/xylazine animals.

Our Conclusion

Consideration should be taken when selecting anesthetics for the guinea pig cardiovascular model. Sodium pentobarbital should be the anesthetic of choice when screening compounds for the potential to prolong QTc interval.

Filed under: Anesthetized Models, Telemetry | No Comments

PAH Spotlight: Small Species with Dual Pressure Telemetry

Posted by CorDynamics on July 23rd, 2013

by Dr. Michael Gralinski, CorDynamics CEO

We continue to expand our capabilities in pulmonary arterial hypertension, and one thing is for certain: surgically instrumenting rats to measure systemic blood pressure AND pulmonary artery pressure—simultaneously—is an effective model for clients researching both prevention AND intervention of PAH.

To obtain continuous recording of pulmonary artery pressure, a telemetry catheter is placed into the pulmonary artery via the right ventricle. Post-recovery, the subjects are then exposed to classic PAH initiation agents such as monocrotaline or newer methods like hypoxia/semaxanib.

Measuring multiple pressures simultaneously allows our experts to differentiate test article effects on the pulmonary vasculature from those on the systemic circulation.

Up until recently, this level of in vivo telemetry instrumentation was only available in large animal models.

View Data Set #1

 View Data Set #2

Efficiency All-Around

At the risk of being obvious, the ability to measure multiple pressures clearly saves time and effort all around.

In addition, our low technical failure rate and clinical observations consistent with the development of robust pulmonary hypertension makes this an efficient option in terms of technician time as well as overall study deliverables.

As always, our models are designed with the 3R’s in mind. Collecting multiple variables from the same experimental subject reduces the need for redundant groups when separate pressures are interrogated.

Filed under: Drug Safety Services, Pulmonary Arterial Hypertension | No Comments

Heart Failure Success Poses Complexities for Drug Developers

Posted by CorDynamics on February 28th, 2013

We covered the complexities surrounding heart failure drug development in a blog we published last summer.  In it, we pointed out:

 Once developers clear the hurdle of finding a compound with promise, the bar is set high for proving their efficacy and superiority over existing drugs to gain regulatory approval.

 Most heart failure medicines have to go through a variety of different measures for efficacy. One of which is “quality of life” as measured by the American Heart Association ratings for heart failure.

For example: Can bedridden patients begin to get out of bed and move around more?

Unfortunately for researchers working on spironolactone, recent reports illustrate this case in point.

In patients experiencing heart failure with preserved ejection fraction, spironolactone did in fact demonstrate improved left ventricular diastolic function but did not have any effect on heart failure symptoms, quality of life, depressive symptoms or hospitalizations.

Although the trial did show improvements in diastolic abnormalities of the left ventricle, the lack of clinical improvements means researchers will most likely conduct further studies, perhaps with patients in more advanced stages of heart failure.

We work in the area of heart failure discovery with some clients who are taking a more non-traditional approach to treating this condition. An example of this would be using dual pharmacology involving both increasing heart function while simultaneously reducing the extrinsic burdens.

 

Filed under: Drug Discovery Services, Heart Failure | No Comments

5 Signs Drug Development Outsourcing is In

Posted by Theresa Gralinski, Marketing Director at CorDynamics on November 14th, 2012

I spent most of last week at the American College of Toxicology meeting in Orlando taking the industry’s proverbial temperature.

Over the last four years this meeting’s attendees seemed concerned about feverishly downsizing, feverishly cutting budgets or feverishly outsourcing. People just didn’t feel well. This year attendees seemed to be “feeling” healthy and more optimistic.

Preclinical CRO Drug Development Outsourcing

I saw five clear signs that industry outsourcing is officially IN.

1. Back to Business—With mass waves of downsizing behind a number of our colleagues, clients and competitors, the focus of discussions turned to current programs and upcoming projects.

2. Changing Roles—Longtime  friends were embracing new positions, translating their pharma drug safety and drug discovery experience into success at virtual biotechs or contract research organizations.

3. New CROs and Consultants Join the Ranks—We welcomed new CROs to the “club” and I met with quite a few toxicologists who have decided to work as consultants to share their expertise to meet the anticipated demand.

4. Buzzwords—Collaboration. Customized. Experience. Responsive. Did I say collaboration?

5. Social Media…Really?—Admittedly the industry is still skeptical of the idea in a regulated industry. However with more drug developers looking for external services, vendors and CROs want to be easily found. (Shameless examples: cardiovascular CRO, prolonged QT interval, cardiovascular pharmacology.) Social media is a good way to get the message out.

I polled attendees on their comfort levels with the top social media platforms. Results: LinkedIn=Great; Blogging=Good; Twitter=So-So; Facebook=No Thanks.

Did you get a different temperature reading from the meeting? Or, did you sense a healthier optimism as well? Feel free to comment here or you can find me on Linkedin.

 

Filed under: Drug Discovery Services, Drug Safety Services, Preclinical Consulting Services | No Comments

Timelines and Technology Drive Drug Development

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on October 05th, 2012

Safety Pharmacology Society 2012 Meeting Reveals the “New Normal”

I’m on my way back from a trade show exhibit at the Safety Pharmacology Society meeting in Phoenix. Four days in the desert were filled with sessions, events as well as many friends and colleagues stopping by the CorDynamics booth to say hello.

It didn’t hurt that my business partner Peter Senese once again claimed the prime booth space—as greeter to all—right inside the exhibit hall entrance. We opened up with a vendor show where we were airing Monday Night Football live. A consistent group enjoyed the game over a beer or two, and shared insight into the current state of their organizations.

New Normal

Attendance was down a bit from previous meetings. The continuing consolidations, mergers, and belt-tightening by nature reduced the size of representation from more than a few companies. Nevertheless, the topic seemed to pass as the ‘new normal’ instead of being the focus as years before.

Positive Signs, Rational Approach to Forward Progress

Clients stopped by to discuss their unique drug development projects. Overall, their questions came down to two general categories.

  1. Timelines—When can our new project be initiated? When can we expect results?
  2. New Technology—Are CorDynamics’ new technologies generating solid data? How can we incorporate small animal dual pressure telemetry into our studies? Can we screen for cardiovascular liability in guinea pigs?

Leaving the plus 100-degree weather for the tempered fall of Chicago, we’re coming back with good feelings for the remainder of 2012. Happily, new projects continued to flow into the labs during our absence.

We look forward to next years’ SPS meeting in Rotterdam, Netherlands. Word is that Peter already claimed our lead-in booth space. Hope to see you there.

Filed under: Drug Discovery Services, Drug Safety Services, Langendorff Heart, Telemetry | 2 Comments

Who Regulates Drug Safety and Drug Development Better—the FDA or the EMA?

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on September 26th, 2012

The answer: It depends on who you ask.

The FDA versus the EMA (European Medicines Agency) is a continual debate. Different analysts have different opinions that seemingly change weekly.

 

What is true, is that both the FDA and the EMA have:

• the tough job of regulating drug development to ensure the approval safe and effective therapies.
• their own set of policies, procedures and guidelines.
• their own governing bodies, growing bureaucracies and shrinking budgets.
• vigilantly regulated drug safety with a keen eye on cardiovascular safety.

Yet with all this in common, why do the FDA and EMA sometimes come to different conclusions?

Many say it’s because the healthcare environments are different between the US and Europe, as well as their vastly different legal systems.

Case Study #1: FDA Says Ok, EMA Says No Way
The weight loss drug, Qysmia, earned FDA approval in July. BUT, Qysmia’s sponsor expects the EMA to recommend against approval based on numerous concerns, including the effects of one of the drug’s two main ingredients, phentermine, and the link to possible heart valve damage.

Case Study #2: EMA Says Yes, FDA Says Not Yet
An advisory panel recently recommended approval of the new anti-clotting drug Eliquis. BUT, the FDA rejected the drug for the second time this past June, citing the need for more information.

What to do?
Outsource to contract research organizations experienced with the ins and outs of both agencies and their specific guidelines—especially when it comes to cardiovascular issues.

I know the FDA. Fortunately, my colleague, Dr. Franz Hock, knows the EMA. While neither of us is so bold as to claim the ability to predict FDA and EMA decisions, we do typically know what cardiovascular questions they will ask and what information they will need to make their decisions. Once you know that, finding the answers gets a bit easier.

Filed under: Drug Safety Services, Preclinical Consulting Services | No Comments