Clinical trial NCT03399435 (phase 1, status: terminated)
Conditions: anesthesia, anesthesia, local, analgesia
ICD codes: R20.0, T88.51XS, J95.4, T88.2XXS, T88.51XA, T88.51XD, T88.59XS, O89.3, O29.3X1, O29.3X2, O29.3X3, O29.3X9, O74.4, P04.0
Drugs: bupivacaine low (c3), bupivacaine high (c4), neosaxitoxin (t3)
SMILES: CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C, CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C, NC(=O)OC[C@H]1[C@@H]2NC(N)=N[C@]22N(CCC2(O)O)C(=N)N1O
Reason stopped: 
    the sponsor decided to stop further dosing of healthy volunteers after reviewing the obtained
    efficacy data. the decision is not related to any safety concern.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Subject has given written informed consent to participate.

          -  Male subject, aged 18 years to 55 years, inclusive.

          -  Body mass index between 20.0 kg/m2 and 30.0 kg/m2 inclusive, with a minimal body
             weight of 60.0 kg.

          -  Subject must be in good health as determined by the prior/concomitant diseases,
             physical and laboratory examinations.

          -  Subject must be willing not to donate sperm and to use barrier contraception (condom)
             during sexual intercourse with women from the administration of IMP until Day 90 since
             IMP administration. The subject must be willing to ensure that the female sexual
             partner of childbearing potential uses at least 1 additional method of contraception
             with a low failure rate defined as <1% per year (e.g., oral contraceptives) during
             this time frame. A single barrier method alone is not acceptable.

        Exclusion Criteria:

        At enrollment:

          -  Resting pulse rate <50 beats or >90 beats per minute.

          -  Resting systolic blood pressure <90 mmHg or >140 mmHg. Resting diastolic blood
             pressure >90 mmHg.

          -  Prolongation of QTcF at enrollment, i.e., QTcF >450 ms, or presence of any other of
             risk factors for torsade de pointes or other disturbances of cardiac de- and
             repolarization.

          -  Any out-of-reference range value for the following safety laboratory parameters: GGT,
             serum creatinine, PT, and INR.

          -  Any exclusion range met for urinalysis and the following safety laboratory parameters:
             ALT, AST, ALP, total bilirubin, glucose, LDH, potassium, total protein, sodium,
             calcium, CK, hemoglobin, hematocrit, white blood cell count, and platelets.

          -  Any out-of-reference range value for any other safety laboratory parameter that is
             judged as clinically relevant by the investigator.

          -  Positive or missing virus serology test for HIV Type 1 or Type 2 antibodies and
             antigen, hepatitis B surface antigen, hepatitis B core antibodies, or hepatitis C
             virus antibodies.

          -  Subject received IMP in another clinical trial within 1 month before the Enrollment
             Visit. Depending on the nature of the previous IMP, a longer washout may be needed.

          -  Diseases or conditions known to interfere with the distribution, metabolism, or
             excretion of drugs.

          -  History of orthostatic hypotension.

          -  History of, or at risk of seizures.

          -  Significant cardiovascular, respiratory, neuromuscular diseases, or other systemic
             illness.

          -  Subject with an oxygen saturation of less than 95%, as measured by pulse oximetry, or
             subject with known or suspected respiratory difficulty or any condition that may
             compromise a subject's breathing or ability to maintain adequate oxygen saturation.

          -  Known vocal chord palsy.

          -  Any relevant symptom of neurological dysfunction of the motor and sensory system based
             on sensory and motor function testing. History or presence of symptoms of depression
             or anxiety disorders.

          -  Previous injury or surgery of the involved shoulder in the last 2 years.

          -  Any relevant local abnormality at the targeted area of injection.

          -  Any acute or chronic pain condition requiring ongoing treatment or limiting daily
             activities.

          -  Definite or suspected history of drug allergy, particularly to bupivacaine or other
             local anesthetics, epinephrine, or clinically relevant other allergies.

          -  Evidence or history of alcohol or drug abuse including positive or missing drugs of
             abuse screen.

          -  Regular use of any medication, including herbal remedies or over-the counter
             medication within 2 weeks before enrollment into this trial and anticipated use during
             the course of the trial.

          -  Habitually smoking more than 10 cigarettes, 2 cigars, or 2 pipes of tobacco per day
             within the last 6 months before enrollment in this trial.

          -  Known or suspected of not being able to comply with the requirements of the trial
             protocol or the instructions of the trial site staff.

          -  Not able to communicate meaningfully with the trial site staff.

          -  Employee of the investigator or trial site, with direct involvement in the proposed
             trial or other trials under the direction of that investigator or trial site, as well
             as family members of the employees or the investigator.

          -  Blood loss of 500 mL or more within 3 months before enrollment in this trial.

        On Day -1:

          -  Any relevant deterioration in the health of the subject since the Enrollment Visit
             possibly impacting participation in the trial, including AEs, safety laboratory
             parameters, vital signs, body temperature, ECG, or other safety parameters at the
             discretion of the investigator.

          -  Out-of-reference blood pressure or pulse rate if technical failure can be excluded and
             result is confirmed by at least 1 additional measurement: Systolic blood pressure <90
             mmHg or >140 mmHg, diastolic blood pressure >90 mmHg, pulse rate <50 beats or >90
             beats per minute.

          -  Clinically relevant QTcF interval prolongation, i.e., QTcF interval >450 ms.

          -  Any out-of-reference range value for the following safety laboratory parameters: GGT,
             serum creatinine, PT, and INR.

          -  Any exclusion range met for urinalysis and the following safety laboratory parameters:
             ALT, AST, ALP, total bilirubin, glucose, LDH, potassium, total protein, sodium,
             calcium, CK, hemoglobin, hematocrit, white blood cell count, and platelets.

          -  Any out-of-reference range value for any other safety laboratory parameter that is
             judged as clinically relevant by the investigator.

          -  Positive or missing drugs of abuse screen.

          -  Intake of forbidden medication since the enrollment in this trial.

          -  Participation in another clinical trial since the Enrollment Visit.

          -  Blood loss of 100 mL or more since enrollment in this trial.

          -  Failure to comply with trial requirements, e.g., consumption of alcohol, etc.,
             considered by the investigator to affect subject safety or interfere with the
             integrity of the trial.

          -  Any relevant local abnormality at the targeted area of injection.