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An Initial Study of AZD7325 in Adults With Fragile X Syndrome

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ClinicalTrials.gov Identifier: NCT03140813
Recruitment Status : Recruiting
First Posted : May 4, 2017
Last Update Posted : March 6, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
This study will investigate the safety, tolerability and blood pharmacodynamics of treatment with oral administration of AZD7325 at 5 mg BID, 15 mg BID, and placebo BID, in adults with Fragile X Syndrome. The study also will also investigate measures of efficacy and biomarkers during treatment.

Condition or disease Intervention/treatment Phase
Fragile X Syndrome Drug: AZD7325 (High-Dose) Drug: AZD7325 (Low-Dose) Drug: Placebo oral capsule Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Initial Double-Blind, Placebo-Controlled Two-Dose Crossover Study of AZD7325 in Adults With Fragile X Syndrome
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Placebo - Low-Dose - High-Dose
Placebo AZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.

Experimental: Placebo - High-Dose - Low-Dose
Placebo AZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.

Experimental: Low-Dose - Placebo - High-Dose
AZD7325 5mg BID in gelatin capsules Placebo AZD7325 15mg BID in gelatin capsules
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.

Experimental: Low-Dose - High-Dose - Placebo
AZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules Placebo
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.

Experimental: High-Dose - Low-Dose - Placebo
AZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules Placebo
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.

Experimental: High-Dose - Placebo - Low-Dose
AZD7325 15mg BID in gelatin capsules Placebo AZD7325 5mg BID in gelatin capsules
Drug: AZD7325 (High-Dose)
15mg PO BID

Drug: AZD7325 (Low-Dose)
5mg PO BID

Drug: Placebo oral capsule
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.




Primary Outcome Measures :
  1. Amyloid Precursor Protein (APP) [ Time Frame: Through end of study, approximately 12 weeks ]
    Short-term treatment of peripheral APP dysregulation by correcting elevated levels


Secondary Outcome Measures :
  1. Change in the Social Withdrawal subscale score of the Aberrant Behavior Checklist (ABC) [ Time Frame: Through end of study, approximately 12 weeks ]
    The ABC is the gold standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.

  2. Change in the Pediatric Anxiety Rating Scale (PARS) [ Time Frame: Through end of study, approximately 12 weeks ]
    The PARS is the gold standard parent/caregiver reported anxiety outcome measure for use in Fragile X Syndrome clinical trials.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnostic confirmation of full mutation FXS (at least partial gene methylation).
  • 50 ≥ Age ≥18 years. Males and Females included in study.
  • General good health as determined by physical exam, medical history and laboratory work up.
  • FXS genetic reports at screening
  • IQ less than or equal to 80. Note: IQ cutoff is used as a means to exclude cases of females with FXS who have the full mutation, but may have neurotypical development (ie: do not have the full FXS phenotype despite positive FXS genetic testing) due to variability in X chromosome inactivation patterns.
  • Male study participants who are sexually active with a female partner of childbearing potential must be surgically sterilized, practicing abstinence, or agree to use highly effective methods of birth control (defined in the list below), and not rely on barrier methods and spermicide alone, from the time of screening until 1 week after final dose of study drug. Male study participants must also not donate sperm from the time of screening until 1 week after final dose of study drug. Given that AZD7325 is not mutagenic, there is no mandatory requirement for condom use, either for avoidance of procreation or in the case of treated males with a pregnant partner.
  • Women of childbearing potential may be included in the study provided they are established on, and continue to use, highly effective contraceptive methods from the time of screening until 1 week after the final dose of study drug. Highly effective methods of contraception associated with inhibition of ovulation (either oral, intravaginal or transdermal), progestin-only hormonal contraception associated with inhibition of ovulation (either oral [specifically Micronor, Nor-QD or their generic equivalents], injectable or implantable).
  • Aberrant Behavior Checklist total score of 20 or higher at screening

Exclusion Criteria:

  • Concomitant use of modulators of GABA A neurotransmission. (examples)
  • Use of more than three psychotropic drugs that do not directly impact GABA transmission, and/or unstable dosing of any psychotropic medication in the 4 weeks prior to baseline visit.
  • Subjects are prohibited from use of strong and moderate modulators of CYP3A and CYP2C19 during the screening (at least 2 weeks before initiation of the study) and treatment periods of the study. Such prohibited drugs are outlined in http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf
  • CNS-suppressing agents such as central analgesics, muscle relaxants, benzodiazepines, other sedatives, and should also limit alcohol intake.
  • Unstable seizure disorder as defined by any seizure in the 6 months prior to baseline visit and/or a change in any anti-convulsant drug dosing in the 60 days prior to study entry.
  • All patients with abnormal baseline safety lab assessments including, but not limited to ALT or AST greater than 1.5 the upper limit of normal, total bilirubin or creatinine greater than 1 time the upper limit of normal or other clinically relevant lab abnormality or abnormality in ECG, HR or BP at screening as judged by the investigator.
  • Clinical relevant history or presence of any medical disorder judged by the investigator at potentially interfering with this trial.
  • History of or current abuse of drugs or alcohol including prescription medication.
  • For female subjects of child bearing potential (women 50 & under is "amenorrhoeic for 12 months or more (following cessation of exogenous hormonal treatments - if these have been previously taken) and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range) a positive pregnancy test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03140813


Contacts
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Contact: Stephanie Booker 513-803-2860 stephanie.booker@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Stephanie Booker    513-803-2860    stephanie.booker@cchmc.org   
Principal Investigator: Craig Erickson, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03140813     History of Changes
Other Study ID Numbers: CIN001 - AZD7325 in FXS
First Posted: May 4, 2017    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fragile X Syndrome
Mental Retardation, X-Linked
Genetic Diseases, X-Linked
Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System