And another one bites the dust.... Glad I didn't go into this trial, which I looked at closely.

A futility study showed in several analyses that both doses of the drug that were tested (15 mg and 45 mg) were futile at slowing disease progression, Tanya Simuni, MD, of Northwestern University, and colleagues reported online in the Lancet Neurology.

"Our results show that pioglitazone is unlikely to be efficacious as a disease-modifying intervention in early Parkinson's and therefore is not recommended for further testing for that indication," they wrote. "Although our negative results are disappointing, the design of this futility study is an example of a useful and efficient study design that can exclude a compound unlikely to be successful in larger and more costly phase III studies."

http://www.medpagetoday.com/Neurolog...sDisease/52347

Keep in mind, this is another drug that proved quite successful in curing PD for Mickey Mouse in pre-clinical research.

I dont' understand why they used this diabetes drug when Byetta, another diabetes drug, sounded so promising Anyone know?

Byetta (Exenatide) is also being researched in a separate trial. The phase 1 and early phase 2 results have been encouraging. Exenatide has a totally different mechanism of action than Pioglitazone, so the results can be different. Let's hope.

I don't understand why pioglitazone was "found useless for Parkinson's" when the results showed a mean change in UPDRS score after 44 weeks of:
15mg dose: 4.42
45mg dose: 5.13
placebo: 6.25
Since for UPDRS low scores are good, both sizes of dose were better than for placebo.

There is the possibility that the results do not show statistical significance, but that is not the same as showing the drug is useless. There is the possibility that the trial had a minimum expected improvement (say a UPDRS difference of 4 points) which was not met. But again that is not the same as proving uselessness.

I think we are in danger of throwing out potentially useful therapies. I'm now 10 years post diagnosis so a therapy that had only slowed down my progression by 10% would have made a big difference for me.

In general, what are the chances that a new therapy would pass a clinical trial which this profile:
x% improvement in y% of people and z% worsening in the rest.

John

John, I agree with you, the headline of the article was somewhat extreme, which is typical of news reports. In actuality, there was some degree of "statistical significance" in the results. The problem, as you suggested, was the difference didn't reach the pre-required "practical" difference, which was a minimum of 3 points (you were close). There were also many other measures taken and, again, these were not statistically, or practically different. Interestingly, sensitivity analysis showed the opposite results than did the primary analysis.

Nevertheless, you would think that with some positive results, there would be room to consider further investigation. I think there are three reasons this is not happening. First, given the nasty side effects associated with pioglitazone, I doubt any PD patient would consider taking it even if we knew for sure that we would slow progression by one point on the total UPDRS over the cause of a year (practical significance); second, I think the science community right now thinks there is greater hope that Exenatide will have some efficacy with fewer side effects; and finally, as pioglitazone is already a generically approved drug, there is little money to be made by a new use approval so no big pharma is backing the research and pushing it forward.

Just some thoughts.

Study information:
A trial of Exenatide for the treatment of moderate severity Parkinson's disease

Condition category
Nervous System Diseases
Date applied:
24/01/2014

Date assigned
24/01/2014


Overall trial status
Ongoing

Recruitment status
No longer recruiting

Where is the study run from?
The study is being co-ordinated by University College London Clinical Trials Unit. Patients will have an appointment at the National Hospital for Neurology and Neurosurgery - part of University College London Hospitals.

When is the study starting and how long is it expected to run for?
The study will start in June 2014 and end in June 2016. Patient recruitment will finalise in March 2015.

Who is funding the study?
This research is being funded by the Michael J Fox Foundation for Parkinson's Research and the drug is being provided free of charge by Bristol-Myers Squibb/AstraZeneca.
http://www.isrctn.com/ISRCTN75891427