Fragile X SyndromePhase 1NCT03140813
An Initial Study of AZD7325 in Adults With Fragile X Syndrome
A Phase 1 study testing AZD7325 (High-Dose) and AZD7325 (Low-Dose) in people with Fragile X Syndrome, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- AZD7325 (High-Dose) and AZD7325 (Low-Dose)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2018to 18 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnostic confirmation of full mutation FXS
- 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
Who cannot join
- 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 to ≤1 alcoholic beverage per day.
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: An Initial Double-Blind, Placebo-Controlled Two-Dose Crossover Study of AZD7325 in Adults With Fragile X Syndrome
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.
- Conditions
- Fragile X Syndrome
- Being tested
- AZD7325 (High-Dose), AZD7325 (Low-Dose), Placebo oral capsule
- Medical subject headings
- Fragile X Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD7325 (High-Dose)Drug
15mg PO BID
AZD7325 (Low-Dose)Drug
5mg PO BID
Placebo oral capsuleDrug
Placebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration.
| Study group | Role | What they receive |
|---|---|---|
| Placebo - Low-Dose - High-Dose | Experimental | Placebo AZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
| Placebo - High-Dose - Low-Dose | Experimental | Placebo AZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
| Low-Dose - Placebo - High-Dose | Experimental | AZD7325 5mg BID in gelatin capsules Placebo AZD7325 15mg BID in gelatin capsules Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
| Low-Dose - High-Dose - Placebo | Experimental | AZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules Placebo Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
| High-Dose - Low-Dose - Placebo | Experimental | AZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules Placebo Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
| High-Dose - Placebo - Low-Dose | Experimental | AZD7325 15mg BID in gelatin capsules Placebo AZD7325 5mg BID in gelatin capsules Receives: Drug: AZD7325 (High-Dose); Drug: AZD7325 (Low-Dose); Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amyloid Precursor Protein (APP)
Short-term treatment of peripheral APP dysregulation by correcting elevated levels
Measured: Through end of study, approximately 12 weeks
Secondary outcomes (2)
Change in the Social Withdrawal subscale score of the Aberrant Behavior Checklist (ABC)
The ABC is the gold standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.
Measured: Through end of study, approximately 12 weeks
Change in the Pediatric Anxiety Rating Scale (PARS)
The PARS is the gold standard parent/caregiver reported anxiety outcome measure for use in Fragile X Syndrome clinical trials.
Measured: Through end of study, approximately 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start16 Jan 2018
- Primary completion18 Jun 2020
- Study completion18 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ernest Pedapati, MD, Principal investigator, Cincinnati Chlidren's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03140813
- Sponsor's protocol ID
- CIN001 - AZD7325 in FXS
- Status last verified
- Feb 2020
- First submitted
- 17 Apr 2017
- Last updated
- 8 Feb 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Initial Double-Blind, Placebo-Controlled Two-Dose Crossover Study of AZD7325 in Adults With Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT03140813
- Acronym / sponsor ID
- CIN001 - AZD7325 in FXS
- Conditions
- Fragile X Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 16 Jan 2018 (actual)
- Primary completion
- 18 Jun 2020 (actual)
- Study completion
- 18 Jun 2020 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo - Low-Dose - High-Dose | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsulePlacebo AZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules |
| Placebo - High-Dose - Low-Dose | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsulePlacebo AZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules |
| Low-Dose - Placebo - High-Dose | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsuleAZD7325 5mg BID in gelatin capsules Placebo AZD7325 15mg BID in gelatin capsules |
| Low-Dose - High-Dose - Placebo | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsuleAZD7325 5mg BID in gelatin capsules AZD7325 15mg BID in gelatin capsules Placebo |
| High-Dose - Low-Dose - Placebo | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsuleAZD7325 15mg BID in gelatin capsules AZD7325 5mg BID in gelatin capsules Placebo |
| High-Dose - Placebo - Low-Dose | Experimental | Drug: AZD7325 (High-Dose), Drug: AZD7325 (Low-Dose), Drug: Placebo oral capsuleAZD7325 15mg BID in gelatin capsules Placebo AZD7325 5mg BID in gelatin capsules |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Diagnostic confirmation of full mutation FXS
- 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.
Key exclusion criteria (9 listed)
- 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 to ≤1 alcoholic beverage per day.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD7325 (High-Dose)15mg PO BID | Drug | High-Dose - Low-Dose - Placebo, High-Dose - Placebo - Low-Dose, Low-Dose - High-Dose - Placebo, Low-Dose - Placebo - High-Dose, Placebo - High-Dose - Low-Dose, Placebo - Low-Dose - High-Dose |
| AZD7325 (Low-Dose)5mg PO BID | Drug | High-Dose - Low-Dose - Placebo, High-Dose - Placebo - Low-Dose, Low-Dose - High-Dose - Placebo, Low-Dose - Placebo - High-Dose, Placebo - High-Dose - Low-Dose, Placebo - Low-Dose - High-Dose |
| Placebo oral capsulePlacebo will be dosed similar to AZD7325, in terms of dosage form, frequency and duration. | Drug | High-Dose - Low-Dose - Placebo, High-Dose - Placebo - Low-Dose, Low-Dose - High-Dose - Placebo, Low-Dose - Placebo - High-Dose, Placebo - High-Dose - Low-Dose, Placebo - Low-Dose - High-Dose |
Primary outcome
Amyloid Precursor Protein (APP)
Time frame: Through end of study, approximately 12 weeks
Short-term treatment of peripheral APP dysregulation by correcting elevated levels
2 secondary outcomes
Change in the Social Withdrawal subscale score of the Aberrant Behavior Checklist (ABC)
Time frame: Through end of study, approximately 12 weeks
Change in the Pediatric Anxiety Rating Scale (PARS)
Time frame: Through end of study, approximately 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernest Pedapati, MD principal investigator
Cincinnati Chlidren's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD7325 (High-Dose) and AZD7325 (Low-Dose) in people with Fragile X Syndrome, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amyloid Precursor Protein (APP) (time frame: Through end of study, approximately 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2021.