Clinical trial: A Safety Study of NNZ-2566 in Patients With Fragile X Syndrome (NCT01894958)

Eligibility criteria:
Inclusion Criteria:

          1. Fragile X Syndrome with a molecular genetic confirmation of the full FMR1 mutation.

               -  Results from previously completed testing are acceptable with written
                  documentation of the genetic results.

               -  Results from PCR or Southern blot tests are acceptable

               -  Results from cytogenetic testing are not acceptable but subject may be eligible
                  if molecular genetic testing is redone.

               -  A full mutation with mosaicism is allowed if:

                    -  Subject manifests full phenotypic profile of Fragile X syndrome

                    -  CGG Repeats >200 are detected

                    -  Southern blot prevails over PCR, if Southern blot shows >200 repeats and PCR
                       results show <200 repeats.

               -  The following results would not meet criteria:

                    -  Deletions

                    -  Point mutations

                    -  Mosaicism without detection of >200 CGG repeats or absence of full
                       phenotypic profile in an individual with mosaicism

          2. Males, aged 12-45 years

          3. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at
             Screening

          4. Subjects with a total score of 30 or greater on the Aberrant Behavior Checklist (ABC)
             at Screening.

          5. Current treatment with no more than 3 psychotropic medications. This includes
             medications used to treat problems with sleep onset and sleep continuity. Melatonin
             for difficulties with sleep onset is permissible and is excepted from the count of
             psychotropic medications. Similarly, anti-epileptic medications are permitted and are
             not denoted as "psychotropic medications" if they are used for treatment of seizures.
             Use of anti-epileptics for other indications such as the treatment of mood disorders
             counts towards the limit of permitted medications. Concurrent use of omega-3 fatty
             acids is also permissible and does not count towards the allowed number of concomitant
             psychotropic medications. A complete list of permitted concomitant psychotropic
             medications can be found in Appendix A.

          6. Concomitant medications for chronic medical conditions are permissible. Examples of
             chronic medical conditions include gastroesophageal reflux disease (GERD) and asthma.
             Every effort should be made to keep the doses and dosing regimens of these medications
             stable in the 4 weeks preceding Screening and during the period between Screening and
             the commencement of study medication.

               1. Permitted psychotropic concomitant medications (except for anti-epileptic
                  medications-see below) must be stable, in terms of dose and dosing regimen, for
                  at least 4 weeks prior to Screening and must remain stable during the period
                  between Screening and the commencement of study medication.

               2. Anti-epileptic medications must be at a stable dose and dosing regimen for 12
                  weeks prior to Screening and must remain stable during the period between
                  Screening and the commencement of study medication

          7. Behavioral treatments excluding psychotherapy (see exclusion criteria) must be stable
             for 4 weeks prior to Screening and must remain stable during the period between
             Screening and the commencement of study medication

             a. For each enrollee, every effort should be made to maintain stable regimens of
             allowed concomitant medications and allowed behavioral therapies from the time of
             commencement of single-blind study medication until the last study assessment.

          8. Sufficient expressive language capabilities to complete the Expressive Language
             Sampling Task.

          9. Individuals with a history of seizures should have a stable pattern of seizure
             activity in the 3 months preceding Screening.

        Exclusion Criteria:

          1. Treatment within the two weeks prior to Screening with monoamine (MAO) inhibitors,
             lithium, minocycline, acamprosate, racemic baclofen, investigational metabotropic
             glutamate receptor subtype 5 (mGluR5) medications, d-cycloserine, oxytocin,
             carbetocin, tricyclic antidepressants and bupropion.

          2. Patients planning to commence psychotherapy, including cognitive behavior therapy
             (CBT), during the period of the study or those who had begun psychotherapy, including
             CBT, within 6 weeks prior to Screening.

          3. History of, or current, cardiovascular, renal, hepatic, respiratory and/or
             gastrointestinal disease, which may interfere with the absorption, distribution,
             metabolism or excretion of the study medication, or which may interfere with the
             interpretation of the safety/tolerability or efficacy of the study medication.

          4. History of, or current cerebrovascular disease or clinically significant brain trauma.

          5. History of, or current clinically significant endocrine disorder, e.g. hypo or
             hyperthyroidism, or diabetes.

          6. History of, or current malignancy.

          7. Current major depressive disorder (patients have to be free of the most recent episode
             for 3 months prior to enrollment).

          8. History of a DSM-5-defined substance use disorder in the 3 months prior to Screening.

          9. Clinically significant abnormalities in safety laboratory tests, vital signs or ECG,
             as measured at Screening.

         10. QT/QTcF Exclusions (any of the following):

               -  QTcF > 450 msec. Three ECGs should be obtained at the time of Screening, 5
                  minutes apart from each other, and the results should be averaged.

               -  History of risk factors for torsade de pointes (e.g. heart failure, clinically
                  significant hypokalemia or hypomagnesemia, or a family of long QT syndrome).

               -  A serum potassium at screening <3.0 mmol/L.

               -  QT/QTcF prolongation previously or currently controlled with medication, in which
                  normal QT/QTcF intervals could or can only be achieved with medication

               -  Current treatment with other medications that have demonstrated QT/QTc
                  prolongation and have this risk described in the Warnings and Precautions section
                  of their Prescribing Information

         11. Patients with significant hearing and/or visual impairments that may affect their
             ability to complete the test procedures.

         12. Current treatment with insulin

         13. Hgb A1C values outside of the normal reference range at Screening

         14. Current or past treatment with insulin like growth factor IGF-1

         15. Current or past treatment with growth hormone

         16. Enrollment in another clinical trial within the 30 days preceding Screening

         17. Previously randomized in this clinical trial

         18. Allergy to strawberry
Male
No healthy subjects accepted to join the trial.
Subject must be at least 12 Years old.
Subject must be at most 45 Years

Patient description (medical language): A 15-year-old boy with mild intellectual disability is brought to the office by his parents for a routine physical examination.  The boy is going to a school for students with learning disabilities.  The patient was adopted, and his immunizations are up to date.  Review of the patient's medical records is notable for cytogenetic studies that showed a small gap near the tip of the long arm of the X chromosome, which is consistent with fragile X syndrome, an X-linked disorder. The defect is an unstable expansion of trinucleotide repeats (CGG) in the fragile X mental retardation 1 (FMR1) gene, located on the long arm of the X chromosome. He is not using any medications and vital signs are within normal levels. His blood chemistry analysis as bellow:
Blood Chemistry Value      Normal Range     Patient Value
Glucose                    90-120 mg/dl     95 mg/dl
BUN (Blood Urea Nitrogen)  7-24 mg/dl       10 mg/dl
Creatinine                 0.7-1.4 mg/dl    0.8 mg/dl
Calcium                    8.5-10.5 mg/dl   9 mg/dl
Sodium                     134-143 mEq/L    135 mEq/L
Potassium                  3.5-4.5 mEq/L    3.7 mEq/L
Chloride                   95-108 mEq/L     98 mEq/L
CO2                        20-30 mEq/L      25 mEq/L
Blood pH                   7.38-7.42        7. 39

Patient description (patient's own words): My husband and I brought our 15-year-old son to the clinic for his routine exam. My son is going to school for special needs students. We adopted him a few years ago. His vaccinations are up to date. He already passed some chromosome testing and they found that he has a fragile X syndrome. The doctor told us that it comes from repeats in the fragile X chromosome. My son is not using any medication and his blood pressure temperature and breathing were normal during the exam. He also did a blood test. The results came back and showed that his blood sugar urea creatinine calcium sodium potassium chloride CO2 and blood pH were all within the normal range.

Does the patient match the trial criteria? Entailment