Name of Compound *
Telmisartan (brand name Micardis)
Name of Proposer *
Philip Neustrom
Company Name (if applicable)
Generic medication, no applicable company name.
Phone
(Provided on form)
Email*
(Provided on form)
1. What is the scope of this submission?
Treatment Phase 3
2. Please classify the submission according to UK-CTAP Sub Group.
Please select one choice. Please note we reserve the right to change the category recommendation during due diligence.
Renin-Angiotensin-Aldosterone Axis
3. At what stage of development is the compound?
Please select all that apply. Please note that data can be attached in PDF or MS Office formats at the bottom of this form.
- In vitro efficacy data
- In vivo efficacy data
- Confirmatory clinical trials
4. Is the proposed drug/compound currently a UK licensed medicine?
Yes
5. Is the drug/compound licensed elsewhere?
Yes
6. Has the proposed drug already shown preliminary efficacy in COVID-19?
Yes.
7a. Is this compound being tested in any other clinical trials for COVID 19?
Please provide details and trial identifiers (e.g. clinicaltrials.gov or EudraCT). Links may be added below.
There are many trials of de novo initiation of ARBs as COVID-19 treatment; for a list please see https://encycla.com/List_of_COVID-19_ARB_trials (includes links to clinicaltrials.gov).
For telmisartan in particular, there
<important note about current trials' limitations and need for large, pragmatic trial>
7b. Trial Link
Please include the link to the trial information if possible (e.g. clinicaltrials.gov or EudraCT).
8. What are the compounds' therapeutic target(s) and its mechanism of action? *
Please provide as much evidence as possible supported by key references. Additional PDF documents may be attached at the foot of this form.
9a. Is there a credible link between the therapeutic target(s) and COVID-19? *
Please discuss the expression/availability of the therapeutic target in the context of COVID-19 disease progression.
9b. At what stage of disease, based on the WHO ordinal scale for clinical improvement, would the product likely be administered? *
10. What is the expected level of target engagement, physiological response or disease modulation that is necessary for COVID-19 treatment?
11. For compounds that have not been used in humans or previous clinical trials, is preclinical pharmacokinetics and distribution data available?
Please provide data or reference to animal plasma and tissue pharmacokinetics data along with a brief description of methods (dose, dosing interval, analytical method). Please attach PDFs at the foot at the form as necessary.
12. Please provide a rationale for dose selection. *
If available, provide details of pharmacometric assessments relative to in vitro or in vivo defined target exposures.
- Need high dose
- High dose safe in normotensives
80mg telmisartan bid
This dose of telmisartan is expected to give high 24-hour blockade of AT1R. In animal studies of ARBs for viral lung injury and other <<things>>, ARBs are dosed to provide near maximal blockade of AT1R.
For an overview of some relevant animal studies and how the dosing compares to current human trials, please see https://encycla.com/Dosing_ARBs_for_COVID-19.
13. What is the compound’s route of administration, and does this differ from its currently licensed route? *
If possible, please provide data or reference to human pharmacokinetics data. Please attach PDFs at the foot at the form as necessary.
Regular oral administration, as approved.
14. Please provide details on any non-clinical efficacy data with relevance for COVID-19?
Please include details of cell systems employed, multiplicity of infection, preincubation duration, concentration range tested, concentration of protein/serum and resulting EC90 data (or equivalent for non-antiviral medicines).
15. Please provide details of any clinical efficacy data supporting application of the drug for COVID-19 (either in terms of the pathogenesis of the disease and/or its complications).
If clinical efficacy data from another indication is reported, please discuss the relevance of this data for COVID-19.
16a. Which clinical efficacy end point should be evaluated in the context of the proposed drug and its mechanism of action in COVID?
Please select all that apply.
16b. Why have you chosen this clinical endpoint? *
If you selected 'other' for question 16a please explain the clinical endpoint you have chosen.
17. Is there any GLP toxicology data available? Please provide a summary of GLP toxicology data relevant to the intended route of administration and duration of exposure.
18. What is the product’s safety profile? *
Please include information on the risk of drug drug interactions and outline any risk mitigation strategies.
The usual safety risks of ARBs apply. As an approved drug with a long safety record, its safety profile is very well defined.
Include some obvious details, e.g...
Hyperkalmia, reduced renal function, pregnancy..
19. What is the product availability - for trial and in terms of patient numbers which could be treated in the UK?
Telmisartan is a widely available generic drug in the UK and throughout the world.
20. What is the stage of manufacturing and likely scalability of production and supply?
Please include details of active pharmaceutical ingredient (API), finished pharmaceutical product (FFP) specifications, known and potential impurities, stability data supporting a reasonable shelf-life for clinical evaluation (P.T.O), and considerations for downstream scale up if needed.
Approved, readily available generic drug produced by many manufactures.
21. Please provide details of any considerations/concerns for the proposed therapy regarding its administration in the community or in a clinical trial by healthcare staff.
(e.g. special training, logistics, devices)
If used in an outpatient setting, it may be useful to have patients monitor their blood pressure at home.
22. Please provide any other information you feel is relevant to the compound/drug assessment.
Data Consent *
By selecting yes you are agreeing to the collection, retention and sharing of data for the purpose of progressing this submission through UK-CTAP and, if appropriate, into publicly funded trials.
Publishing of Recommendations *
If your proposal is recommended into trial UK-CTAP would publish its decision for transparency. If you have a legitimate case for not publishing please attach a document outlining your reasons. This will not affect the progress of your proposal.
