adverse events of special interest (aesls) -adults...mar 10, 2017 · paralysis flaccid,...

Dear Physician,

Manual for Active Questioning of AESis -AdultsClinical Study MRZ 60201/SP/3001

Version 1.0

Manual for Active Questioning of Adverse Events of Special Interest (AESls)

-Adults -

10 Aug 2011

Please take time to perform the assessment without any interruption. The following description of AESI terms should help you to find out if any areas of the body away from the injection site were affected and caused symptoms of toxin spread.

Important: In general, please ensure that

• you focus only on the AES/ terms listed in the protocol and the case report form (CRF) for this study (see also table below)

• the date of this active questioning for signs and symptoms of potential toxin spread is noted in the subject's file for each visit performed; signs and symptoms will be questioned for the period since the last visit/phone call

• for every symptom affirmed by the subject and/or the subject's guardian/caregiver a respective entry (AES/ term) is documented in the subject' file and an AE page of the CRF is filled out

• an AES/form is completed and sent to the CRO (please refer to the contact data given on the AESI-form) within 24 hours. The AE form in the CRF as well as the CRF pages for medical history/concomitant disease(s), and for previous and concomitant medication and therapies shall be /axed along with the AES/ fax form

• a focused physical/neurological exam for every symptom listed and reported by the subject and/or the subject's guardian/caregiver is performed and the appropriate box on the AES/ CRF page to indicate if the examination was done is checked

• any worsening of a pre-existing condition (already present and recorded at screening) or any new symptom which has been observed during active AES/ questioning has to be documented as an AES/ as well (procedures as indicated above)

CONFIDENTIAL AND PROPRIETARY The contents of this document are confidential and proprietary to Merz Pharmaceuticals GmbH.

Unauthorized use, disclosure or reproduction is strictly prohibited. This document or parts thereof may not be disclosed to parties not associated with the clinical investigation without the prior written consent of Merz Phannaceuticals.

of5 This questionnaire is owned by Petra Weissenberger (©P. Weissenberger/Merz Pharmaceuticals GmbH)


Version 1.0 10 Aug 2011

Body System AESI (alert term) Cardiovascular disorders Bradycardia

Eye disorders Accommodation disorder, Eyelid function disorder, Eyelid ptosis, Pupillary reflex impaired, Diplopia, Extraocular muscle paresis, Vision blurred

Gastrointestinal disorders Constipation, Dry mouth, Dysphagia, Ileus paralytic

Infections and infestations Botulism Musculoskeletal and connective tissue Muscular weakness, Pelvic floor muscle weakness disorders Nervous system disorders Areflexia, Bulbar palsy, Cranial nerve palsies

multiple, Cranial nerve paralysis, Dysarthria, Facial palsy, Facial paresis, Hemiparesis, Hypoglossal nerve paresis, Hyporeflexia, Hypotonia, Illrd nerve paresis, IV th nerve paresis, Monoparesis, Paralysis, Paralysis flaccid, Paraparesis, Paresis, Paresis cranial nerve, Peripheral nerve palsy, Peripheral paralysis, Quadriparesis, Speech disorder, Trigeminal nerve paresis, Vocal cord paralysis, Vocal cord paresis

Renal and urinary disorders Urinary retention Respiratory, thoracic and m~diastinal Dyspnoea, Diaphragmatic paralysis, Dysphonia, disorders Respiratory arrest, Aspiration, Pneumonia

aspiration, Respiratory depression, Respiratory failure

AESI: Adverse event of special interest

During each visit or telephone contact the occurrence of Adverse Events of Special Interest (signs or symptoms of potential toxin spread) will be assessed by active questioning. It should be attempted to obtain as much information as possible from the subject directly except the subject has a severe cognitive impairment. Then the questions should be raised to the subject's guardian/caregiver. In case of a telephone contact, the physician shall seek to speak directly to the subject and the guardian/caregiver (if applicable) with the help of the speaker function of the phone.

CONFIDENTIAL AND PROPRIETARY The contents of this document are confidential and proprietary to Merz Phannaceuticals GmbH.

Unauthorized use, disclosure or reproduction is strictly prohibited. This document or parts thereof may not be disclosed to parties not associated with the clinical investigation without the prior written consent of Merz Phannaceuticals.

of 5 This questionnaire is owned by Petra Weissenberger (©P. Weissenberger/Merz Pharmaceuticals GmbH)


Version 1.0

1. Questions related to eye function:

Related AESI terms:

10 Aug 2011

Accomodation disorder, vision blurred, diplopia, extraocular muscle paresis, Hird nerve paresis, IVth nerve paresis, pupillary reflex impaired, eyelid function disorder, eyelid ptosis

Did you have more problems or changes with vision, double vision, drooping of the eyelid? Did you have more sensitivity (touchiness) to light (did you need to wear your sunglasses more often?)? Did you have problems with reading?

Are any of these problems new to you or have become more severe or have changed since we spoke/I saw you last time?

2. Questions related to chewing/tongue:

Related AESI terms: Bulbar palsy, hypoglossal nerve paresis, trigeminal nerve paresis

Did you have increased difficulties with chewing? Did you have more frequent tongue bites or newly problems to stick your tongue out? Did you experience the feeling of a 'heavy tongue'?

Are any of these problems new to you or did become more severe or have changed since we spoke/I saw you last time?

3. Questions related to voice:

Related AESI terms: Dysphonia, bulbar palsy, dysarthria, hypoglossal nerve paresis, speech disorder, vocal cord paralysis, vocal cord paresis

Did your voice sound different? Did you have trouble speaking? Did your voice become hoarse? Did your voice become more breathy? Did your voice become quieter (e.g. change or loss of voice, trouble saying words clearly)? Did you have difficulties or are you no longer able to whistle?



Unauthorized use, disclosure or reproduction is strictly prohibited. This document or parts thereof may not be disclosed to parties not associated with the clinical investigation without the prior written consent of Merz Pharmaceuticals.



Version 1.0

4. Questions related to mouth/throat/bowel:

Related AESI terms: Dysphagia, dry mouth, constipation, paralytic ileus, bulbar palsy

Did you notice more problems with swallowing? Did you have to drink more than before to be able to swallow solid food? Did water come out of your nose during drinking? Did you have to cough during swallowing?

10 Aug 2011

Did you have an increased dryness of your mouth, constipation (harder stools) or bowel disturbances (sluggishness of the bowels)? Has the number of bowel movements changed?


5. Questions related to heart function:

Related AESI term: Bradycardia

Did you feel light headed or faint? Can you feel your heart beat? Did your heart beat become slower than before?


6. Questions related to lung function:

Related AESI terms: Dyspnoea, diaphragmatic paralysis, respiratory arrest, aspiration, pneumonia aspiration, respiratory depression, respiratory failure

Did you have problems with breathing or shortness of breath (feeling breathless)? Did you have 'wet sound'/'rattling' while breathing? Did you still have a cough or even pneumonia due to something went down the wrong throat?






Version 1.0

7. Questions related to bladder function:

Related AESI term: Pelvic floor muscle weakness, urinary retention

10 Aug 2011

Did you have problems with bladder control (holding of urine, leak of urine or unintended urination)? Did you have problems with passing water or bladder emptying?


8. Questions related to muscle function/strength:

Related AESI terms: Cranial nerve palsies multiple, cranial nerve paralysis, paresis cranial nerve, trigeminal nerve paresis, monoparesis, muscular weakness, paralysis, paralysis flaccid, paresis, peripheral nerve palsy, peripheral paralysis, facial palsy, facial paresis, areflexia, botulism, hyporeflexia, hypotonia, quadriparesis, hemiparesis, paraparesis

Did you feel weakness in body parts that have not been treated? Did you have the feeling of a loss of strength in local body areas e.g. , face, arm[s] , leg[s] , one side of the body, upper/lower half of the body? Did you have the feeling of a loss of strength all over the body? Did you have increased motor/movement problems, start tripping or falling (walking problems) or dropping of things (gripping or holding problems)? Did you have difficulties to make a face?


If any of the above symptoms of a body system have been newly affirmed by the subject or the subject's guardian/caregiver or have been confirmed as worsened, a focused physical/neurological exam needs to be performed to confirm whether an AESI needs to be recorded. In case of a telephone contact the physician has to decide if the subject needs to be seen for an optional safety visit or if this is not possible by the family doctor in order to perform a focused physical/neurological exam and to decide if treatment for the event should be started.



of5 This questionnaire is owned by Petra Weissenberger (©P. Weissenberger/Merz Pharmaceuticals GmbH)

adverse events of special interest (aesls) -adults...mar 10, 2017 · paralysis flaccid,...

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