Entries by Andrew Sonderfan

Experience with rhabdomyolysis?

Hi RTC colleagues -

A client with whom I just began working has a compound in their library that appears to elicit rhabdomyolysis. They're curious about the mechanism, and whether it's an on- or off-target effect, as they consider whether this may be an anticipated liability should they pursue other compounds with similar structure or function.

Anybody seen much of this, and/ or have insights to share? I'd be happy to connect you directly (I'm sure I'd learn something from the discussions).

Thanks; best wishes,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

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Reminder – RTC Business Practices Survey (closes Friday, June 11)

Dear Membership -

Thanks to all who have completed the survey - around 50 respondents so far which is encouraging.

If you haven't already, please take a few moments to provide your input - it's helpful to everyone.

To complete the Survey, lease (1) log in to the RTC website and then (2) follow this link to access the survey:

www.toxconsultants.com/eforms/2020-rtc-business-practices-revenue-survey/25/

Thanks for your participation!

Andy Sonderfan
For the EC
...

 

[14C]-AME in rats. Covance Madison or… (?)

Hi RTC -

It's been several years since I conducted a radiolabeled study (with QWBA, metabolite ID, etc.), and that study was at Covance Madison (they did an excellent job).

Prior to that it was several years between similar studies, but the previous study was also at Covance Madison (and was well done).

Now I'm planning to obtain proposals for a [14C] study - definitely I'll contact Madison. I can't recall other CRO(s) where I may have earlier obtained competitive quotes. Whom would you recommend?

Thanks,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

IND with draft; final report within 120 days for…..SAFETY PHARMACOLOGY?

Dear RTC experts -

I have a client that earlier completed GLP toxicology (but not Safety Pharmacology) to enable a first-in-human study outside the ICH regions. The completed tox will suffice for the limited-scope clinical program to be undertaken when the US IND is filed toward the end of this calendar year. Here's the question - we're conducting Core Battery SP studies to be included in the IND submission, and the client asked "Can we submit the IND with draft SP reports, and then finalize them within 120 days?"

I'd never encountered this question (when performed together, SP studies are always finalized ahead of the repeat-dose tox, so the situation never arose). I checked out FDA's (2000) Guidance, and it seems specific to "toxicology report" (which may be submitted as a draft, though with signed pathology as a later-added but well-understood stipulation).

Draft Safety Pharm reports? Your experiences and advice are welcome!

Thanks,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Reminder – 2020 RTC Business Practices Survey

RTCers -

Many of you have already completed the 2020 RTC Survey - great! If not, please take a few moments to provide your input: your experiences and opinions help your fellow Members.

Log in and follow this link for more info (or look for the email you received on May 10):
https://www.toxconsultants.com/newsletter/2020-survey/

Thanks!
Andy Sonderfan
For the EC...

 

Monkey muscle histopathology expertise

Dear colleagues -

I'd appreciate hearing of one or more pathologists with experience evaluating muscle histopathologic changes, particularly in cynos.

Thanks; best wishes,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Pathologist with rodent (esp. kidney) experience?

Dear RTC Colleagues -

A friend who's not (yet!) a client asked if I could facilitate connection with a pathologist that has rodent histopath expertise, especially knowledge of kidney pathology. I know a few pathologists whom I've enjoyed working with for peer reviews, but I'm thinking one or more folks here might know a kidney expert. Can you assist?

Thanks; cheers,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138
...

 

Vendor Qualification?

Dear RTCers -

How often (and under what circumstances) have you or your client formally conducted qualifications as part of selecting a CRO to conduct key GLP nonclinical studies? I had a program manager at a client company ask about this in passing (they're a small company owned by a Very Large pharma company).....and for sure, the parent company has formal procedures in place for qualifying clinical as well as nonclinical CROs.

Thanks to all,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Design strategy for a 13-week combination tox in rats – your thoughts?

Dear RTCers -

I have a client who plans to conduct a 13-week combination study in rats. The study will evaluate the combination of a marketed small molecule with the client's new small molecule: the two compounds are planned to be administered, sequentially, once-daily in planned clinical trials.

The plan is to evaluate a vehicle (innovator vehicle followed immediately by marketed-cpd vehicle); low-, mid-, and high-dose combo, and a single-agent group for each of the two compounds (total 6 groups).

Here's the question: Because the clinical safety (indeed, nonclinical safety too) of the marketed compound is well-established, we're considering keeping the dose of the marketed compound the same ("Standard; Std") while varying the dose of the new compound. So the design would be -

Option 1
========================
Vehicle, vehicle
Low(new), StdDose (marketed)
Med(new), StdDose (marketed)
High(new), StdDose(marketed)
High(new)
StdDose(marketed)

Another possibility is to vary the dose of both the new and marketed compound, so -

Option 2
====================
Vehicle, vehicle
Low(new), Low(marketed)
Med(new), Med(marketed)
High(new), High(marketed)
High(new)
High(marketed)

To me, Option 1 seems the better design (minimizes variables; allows more complete characterization of dose-response for new compound.

Have you had experience with design and conduct, and regulatory review, of either or both of these designs? What do you recommend?

Thanks; best wishes,
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138

...

 

Following up: Number of animals for chronic tox studies

Hi RTC colleagues –

I wanted to follow up on Barry's November posting about numbers of animals on chronic tox studies. ...I wish that adding a comment would "bump" the thread to the top of the TalkList so folks would see when there are new comments. Something to consider....

I’ve got a couple of longer-term studies for a non-oncology indication, and preliminary feedback suggests the CRO IACUC is unhappy with numbers (will learn details soon….holidays).

For the rat study (6 months total dosing) I have an interim necropsy at 3 months with 10 rats/ sex in each group, then 20 additional going to 6 months: 15 for terminal necropsy and 5 for recovery.

For the dog study (9 months total dosing) I have an interim necropsy at 3 months with 3 dogs/ sex in each group, then 6 additional dogs going to 9 months: 4 for terminal necropsy and 2 for recovery.

Does this seem appropriate to folks? In my experience (admittedly limited) animal numbers at 30 days are similar to 28 days (i.e., subchronic) and, though numbers at terminal necropsy for the chronics are higher, recovery from a chronic necropsy is the same size as subchronic recovery.

Thanks!
Andy

Andrew J Sonderfan, PhD, DABT
Nonclinical Strategies, LLC
asonderfan@gmail.com
+1.978.505.7138...