Orudis (Ketoprofen) is the oral form of this NSAID. Oruvail is the long acting cousin. A subsidiary of Alpharma has agreed to pay Germany's IDEA up to $202 million in upfront fees and milestones for the U.S. rights to the late-stage pain drug Diractin (ketoprofen in Transfersome gel), a prescription topical NSAID. The license includes access to IDEA's Transfersome technology platform, which delivers drugs locally to targeted areas. IDEA gets $60 million of that sum up front, $77 million in near-term milestones and up to $65 million conditioned on U.S. approval. IDEA is covering the costs of studying the drug, which is currently in Phase III.
"Diractin is the first of many targeted products with reduced side-effects that we see coming from the exploitation of the powerful Transfersome technology platform," commented John Mayo, joint managing general partner of Celtic Pharmaceutical Holdings, a private equity firm.
Celtic Pharmaceutical Holdings L.P. ("Celtic Pharma"), the global private equity firm focused on the biotechnology and pharmaceutical industries, announces that its German portfolio company, IDEA AG has licensed the US rights to its lead product, Diractin® for the treatment of deep pain, to an affiliate of Alpharma Inc. a specialty pharmaceutical company, whose shares are listed on the New York Stock Exchange. Diractin® is a transdermal formulation of ketoprofen which utilizes IDEA's innovative Transfersome® targeted drug delivery platform. Alpharma’s press release is appended to this announcement.
ACR Clinical Classification Criteria for Osteoarthritis of the knee:
Using history and physical examination
Using history, physical examination and radiographic findings:
Using history, physical examination and laboratory findings:
Reference: Altman, R, et al.: Arthritis Rheum 29:1039, 1986.
ACR Criteria for the Classification and Reporting of OA of the Knee
Criteria for classification of idiopathic OA of the knee
Clinical and Laboratory Clinical and Radiographic Clinical*
Knee pain plus at least five of nine:
Age >50
Stiffness <30 minutes
Crepitus
Bony tenderness
Bony enlargement
No palpable warmth
ESR <40 mm/hour
RF <1:40
SF OA
92% sensitive
75% specific Knee pain plus at least one of three:
Age >50
Stiffness <30 minutes
Crepitus
plus
Osteophytes
91% sensitive
86% specific Knee pain plus at least three of six:
Age >50
Stiffness <30 minutes
Crepitus
Bony tenderness
Bony enlargement
No palpable warmth
95% sensitive
69% specific
*Alternative for the clinical category would be four of six, which is 84% sensitive and 89% specific.
RF=rheumatoid factor; SF OA= synovial fluid signs of OA (clear, viscous, or white blood cell count <2000/mm3).
From Altman et al. [1986]; with permission.
Questions
- Indemnification: The sponsor likes to be held harmless for acts of negligence that the PI commits that are solely the error of the treating physician. For example, if a PI treats a subject's UTI during a study and the patient suffers an injury from this, it is squarely the PI's fault and it would not be proper for the sponsor to sustain an injury by being held liable for it. However, we are aware of a BP study where the PI followed the protocol and had the subject wash off their BP medication and suffer a stroke from the lack of the proper BP treatment. The sponsor forced the PI to use his medical malpractice insurance to satisfy the claim for medical malpractice. Clearly, this was an injustice as the PI was following the protocol precisely and even though it is unusual for a stroke to occur during wash out, it certainly does not immunize the subject from having a stroke. When a stroke occurs during wash out it is important that the sponsor take responsibility for the liability. This should be true of any injury ex officio of changing a subject’s treatment while following the protocol. If this drug causes respiratory depression, are you going to be fully liable?
- Study Fully Populated Causing Premature Early Termination: As sites advertise for patients to become research volunteers, the people that are good enough to step forward to join, wash off of their existing treatment, come to our site and devote a significant amount of their time with blood draws, signing paperwork and allowing the experimental protocol to progress, should be guaranteed that the sponsor will not prematurely shut down the study because they have obtained the needed number of subjects. That is, it should be the sponsor's responsibility to do the number crunching early enough not to allow subjects to sign consent and undergo early termination just because the study is now considered full enough. This is not ethical or in the patients best interest. All subjects who sign consent must be allowed to continue thru the protocol if they are continuing to fulfill criteria regardless of how many subjects are in the trial.
- Reimbursement for Screen Failures: Sites are taking finincial risk in the name of enrolling only those subjects who will successfully complete the trial. Sponsors need to recognize that this significantly slows enrollment. When we see a subject who may qualify but then again may not, we would be hesitant to enroll in that study. Since the exclusivity clock starts clicking as soon as the drug is patented it is imperative that the studies are done as quickly as possible. Sites that are rewarded for each piece of work they legitimately perform will have to enroll better. Sites with too high screen failure rates can be turned off to ensure the proper motivation to enroll high quality subjects is present.
- Sponsor Early Term Study: Should the Sponsor ET the study after the site has put a significant amount of work into preparing for it, what finincial arrangements are being thought of to compensate the site? After all, we found the trial, reviewed the IB, isolated potentially eligible subjects and advertised. The rest of the study is the relatively easy part. This goes along with start-up cost reimbursement. There should be a fee paid to the sites for start-up costs to help defray this potentiality. Paying more per subject to compensate for start-up costs leaves the site liable for the costs related to the sponsor unilaterally stopping the trial.
- Initial Fasting Labs and Informed Consent: Many trials have "visit one" with fasting labs and signing informed consent on the same day. This is less desirable than having a visit one where the subject presents non-fasting for the purpose of signing the informed consent form and having the study discussed with them. The potential problem is with a diabetic. If a diabetic patient answers an ad and presents fasting for visit one, a research related procedure was done prior to signing the ICF (Informed Consent Form). They could get a low sugar reaction while driving to the site and suffer an MVA. They may also feel pressured to sign the ICF quickly as they know when the do so they will finally get something to eat. This can be most safely avoided by allowing subjects to sign the ICF on a pre-visit one or by writing protocols that don't have fasting labs as a visit one procedure. Although I understand V1 labs are non-fasting for this trial.
- Recruitment: Too often recruitment is an oversight thought to be the sites problem dealt with at a time other than the beginning of the trial. It becomes the sponsor’s problem after many sites under enroll. Wise sponsors address recruitment up front at the investigator’s meeting and include recruitment agencies. One budget neutral solution is for the sponsor to push to make available an IRB approved ad for those using the central IRB at the very beginning of the trial. In addition use of centralized recruitment agencies like Pi and Acurian can very useful and cost effective. All our databases could be larger. A small minority of people step forward to become research subject volunteers. Planning for recruitment issues at the beginning is much better than catch up at the end.
Qualifying Knee Pain Scores
Mild = 4
Moderate = 5
Severe = 6
Note:
- If the PS (Pain Score) is less than 4, this means the patients has too little pain for the IDEA Drug Study.
- If the PS (Pain Score) is greater than 6, this means the patients has too much pain for the IDEA Drug Study.
- Little variation in pre-study drug exposure PS's.