Design and Implementation of Clinical Plans
Based on several years of experience in taking NCEs into human and up to Proof of
Concept the Clinical Sciences team at Aptuit will work closely with the Client to
design the most efficient Clinical Plan for the Client’s compound, maximizing the
use of innovative and tailored approaches. The Clinical Sciences team will work
with the Client to design clinical plans which can rapidly provide answers to the
key development questions critical for the Client’s investment decisions. Quality,
time and costs are key variables in any project plan; the Clinical Sciences team
will work in close partnership with the Client to make sure that the proposed clinical
plan meets all quality requirements without undue time delays or cost increases.
Design, Conduct, Analysis and Interpretation of Healthy Volunteers and Patients
Studies
Working with an established network of Phase I Units, academic / clinical centres
and Key Opinion Leaders, Aptuit Clinical Sciences can design, conduct, analyse,
interpret and report clinical studies in healthy volunteers and patients. In particular:
- FIM studies (Single Dose & Multiple Dose)
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Single and Fusion protocols (Combined objectives : Single Ascending Dose/Multiple
Ascending Dose + food + relative Bioavailability),
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- Clinical Pharmacology phase I studies
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Safety & Tolerability, Drug Interaction study, Simple and complex PK and Biodistribution
studies,
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- Translational and Experimental Medicine studies
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Earliest Identification of pharmacodynamic readouts & potential surrogate markers
of pharmacological activity,
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Imaging Studies (PET, MRI (structural & functional) EEG, TMS)
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- Phase II clinical studies (Proof of Mechanism/ Concept, Provision of Evidence studies)
Example of Safety & Tolerability Studies
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Sedation
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- Sedation Scales in FTIH
- Multiple Sleep Latency Test
- Cognitive Tests
- Driving Test
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Abuse liability
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- Specific tests in FTIH study
- Abuse Liability Study
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Blood Pressure /
Heart Rate
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- Vital Signs standard in FTIH
- Ambulatory Blood Pressure study
- 24 hrs Holter study
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QT Compliance with the latest regulatory guidelines (FDA, ICH), 21 CFR part 11 compliance
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- Standard ECG in FTIH
- QT/PK study
- Thorough QT study
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Example of Pharmacokinetic Studies
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Drug / Drug Interaction (DDI)
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Study with known substrates of CYP (individual/cocktail approach)
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Study with known inhibitors/inducers
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Absolute bioavailability
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IV/oral in crossover design or simultaneous dosing of stable isotopes
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Food effect / relative bioavailability
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Different treatment arms using a crossover study
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Bioequivalence
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Different treatment arms preferably using a crossover study
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Biodistribution
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Example of Pharmacodynamic Studies
Brain Receptor Occupancy
To evaluate molecular target achievement
To define potential doses for clinical
studies
To assess brain PK
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PET studies with specific ligands
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Challenge Tests
To elicit specific responses in selected populations paradigmatic of the disease symptoms
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7% CO2 challenge in anxious subjects
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public speaking in social phobics (VAS-PET)
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Models
To effectively translate preclinical efficacy data into humans
To evaluate potential dose-responses
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Progressive ratio schedule in drug abusers
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Disturbed sleep model
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Anhedonia model
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Prepulse inhibition in schizophrenics
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Functional brain imaging (fMRI, water-PET, MRS, EEG)
To evaluate specific brain responses in HVs/patients
To study brain neurocircuitries
To assess brain neurophysiology in patients
To produce a brain fingerprint
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Resting state evaluation
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phMRI, phEEG
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Negative affect processing bias in depression
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Cue induced craving
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Delay discounting task
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