| Eligibility |
Inclusion Criteria: Eligibility for this study was met if each one of the following
inclusion criteria was satisfied at Screening (or at baseline when specified):
1. Male or female aged =18 and =50 years.
2. Current diagnosis of schizophrenia or schizoaffective disorder according to DSM-5
criteria as confirmed by the MINI 7.0.2.
3. The following psychiatric criteria were used to determine subject eligibility:
1. Duration of diagnosis of schizophrenia or schizoaffective disorder of =2 years.
2. Outpatient; not hospitalized for worsening of schizophrenia within the last 6
months (partial hospitalization for social management within this time period is
acceptable).
3. Medically stable over the last month and psychiatrically stable without
significant symptom exacerbation over the last 3 months.
4. Stabilized on an oral antipsychotic medication (single agent) for a minimum of 6 weeks
at the time of Screening.
5. On a stable dosage of all permitted non-antipsychotic medications (except for
medication to be used on an as-needed basis) for at least 1 month prior to the
Screening visit and for the duration of the study.
6. CGI-S score of =4 (moderately ill).
7. PANSS score of =80 points.
8. Body mass index (BMI) of =18 kg/m2 and =35 kg/m2.
9. Able to read and understand study procedures and provide written informed consent
before the initiation of any protocol-specific procedures.
10. Willing to comply with all protocol-specified procedures and availability for the
duration of the study.
11. Subject has identified a caregiver or personal contact with whom the subject
communicates with at least once a week.
Exclusion Criteria: Subject will not be considered eligible to participate in this study if
any one of the following exclusion criteria is satisfied at Screening (or at baseline when
specified):
1. Subjects with known clinically significant esophageal or GI disease, including but not
limited to:
1. Known strictures such as esophageal web, pyloric stenosis, or small intestinal
stricture, or subjects with high risk of stricture, e.g., Crohn's disease.
2. Diagnosis of a condition known to elevate or lower gastric pH, e.g., achlorhydria
or hypochlorhydria.
3. Prior varices or small or large bowel obstructions.
4. Prior abdominal or upper gastrointestinal surgery (prior uncomplicated
laparoscopic procedures including appendectomy or colectomy).
5. History of dysphagia or aspiration in the last 5 years.
6. History of an esophageal motility disorder or undergoing treatment for a gastric
motility disorder.
7. Significant history of diarrhea or constipation within 3 months of Screening
8. Multiple episodes of abdominal pain within 3 months of Screening.
9. Subjects who experience moderate or severe dysmenorrhea or menorrhagia (with use
of pain medication) within 3 months of Screening.
10. History of moderate to severe Acid Reflux Disease or a score of =2 on the Acid
Reflux Severity Scale (ARSS) [2], indicating moderate to severe symptoms. The
ARSS scale is as follows:
None = 0 no symptoms Mild = 1 awareness of symptom, but easily tolerated Moderate = 2
discomfort sufficient to cause interference with normal activities Severe = 3
incapacitating, with inability to perform normal activities.
2. Subjects with PILL-5 questionnaire score of 5 or greater.
3. Medical history or current diagnoses indicating the presence of any of the below
conditions:
1. Presence of an uncontrolled, unstable, clinically significant medical condition
could that could put the subject at risk because of participation in the study,
interfere with the subject's ability to participate in the study or influence the
interpretation of safety or PK evaluations.
2. History of a major cardiovascular event (myocardial infarction, cardiac surgery
or revascularization, unstable angina, stroke, or transient ischemic attack) or a
hospitalization for heart failure with 6 months of Screening.
3. Any clinically significant illness, medical or surgical procedure or trauma
within 4 weeks of Screening.
4. Known immunocompromised status, including individuals who have undergone organ
transplantation, on immunosuppression for an immunemediated disease, or are
positive for human immunodeficiency virus (HIV).
5. Subjects with a positive test for active hepatitis B or C at Screening. Subjects
with successfully treated hepatitis B infection which has been resolved for
greater than 1 year or successfully treated hepatitis C infection will not be
excluded.
6. Subjects who have donated more than 250 mL of blood within 30 days of Screening.
7. Subjects who have difficulties with venipuncture/cannulation, including
difficulty accessing veins for blood sampling and/or history of coagulopathy or
endocarditis.
8. Subjects with a current DSM-5 diagnosis of major depressive episode, panic
disorder, agoraphobia, social anxiety disorder, obsessive- compulsive disorder,
post-traumatic stress disorder, generalized anxiety disorder on the MINI 7.0.2 or
in the judgment of the Investigator. (Note that individuals with depression
secondary to schizoaffective disorder are eligible).
9. Suicidal ideation associated with actual intent and a method or plan in the past
6 months, as measured by the C-SSRS (i.e., "Yes" answers on items 4 or 5) at
Screening or having made a suicide attempt within the last 2 years.
10. Known or suspected (non-febrile) seizure disorder.
11. History of neuroleptic malignant syndrome.
12. Current or history of clinically significant tardive dyskinesia.
13. Known or suspected diagnosis of intellectual disability or organic brain disorder
or other diagnosis that is primarily responsible for current symptoms and
functional impairment.
14. Medically non-adherent in the management of their schizophrenia/schizoaffective
disorder.
4. Use of the below medications/treatments in the 2 weeks before enrollment, including:
1. Proton pump inhibitors or H2 blockers.
2. Prokinetic agents.
3. Medications that may interfere with the absorption, metabolism, or excretion of
risperidone, e.g.:
Drugs metabolized via CYP3A4 pathway, such as macrolide antibiotics and azole
antifungals). Moderate or strong CYP3A4 p-glycoprotein (P-gp) enzyme inducers and
inhibitors (carbamazepine, phenytoin, rifampicin, phenobarbital, itraconazole,
verapamil). Moderate or strong CYP2D6 inhibitors (e.g., fluoxetine, fluoxetine
combinations, paroxetine), or quinidine.
4. Concomitant medications, natural remedies, supplements or vitamins which are
associated with changes to gastric motility or pH. Use of antacids is
permissible, except within 2 hours of dosing with LYN-005.
5. Benzodiazepines; except lorazepam, diazepam and oxazepam, which are acceptable if
for the treatment of depression, anxiety or insomnia.
6. Use of more than one antidepressant; or if on just one, a change in dose within 6
weeks of Screening.
7. Depot antipsychotic use within 9 months of Screening.
8. Electroconvulsive therapy within 3 months of Screening.
5. Subjects with clinically significant abnormal safety (e.g. physical examination, vital
sign) or safety laboratory assessments, specifically:
1. Presence of a clinically significant abnormal laboratory result on blood or urine
safety tests at Screening.
2. Anemia (hemoglobin below lower limit of normal reference range) at Screening.
3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =3.0 × upper
limit of normal (ULN), or total bilirubin =1.5 × ULN.
4. Moderate or severe renal insufficiency at Screening (glomerular filtration rate
<60 mL/min, as determined using the Cockcroft-Gault formula).
5. Heart rate of <50 beats per minute (bpm) at Screening.
6. Systolic blood pressure =100 or =150 and/or diastolic blood pressure =60 mmgHg or
=100 mmHg at Screening.
7. HbA1c =6.5% at Screening.
8. Positive fecal occult blood test at Screening
9. Clinically significant prolactin elevation (=200 ng/mL for females; =100 ng/mL
for males).
6. Subjects with the below specified patterns of substance use at Screening:
1. Fulfillment of the DSM-5 criteria for moderate or severe substance use disorder
(excluding nicotine and caffeine) within 6 months of Screening.
2. History of alcohol consumption exceeding moderate use; in males exceeding 21
units per week and in females exceeding 14 units per week (1 unit = 360 ml beer,
25 mL of 40% spirit or a 125 mL glass of wine) over the past month. Subjects are
not permitted to consume alcohol during the inpatient stay nor 12 hours before
any clinic visit while outpatient.
3. Positive ethanol breathalyzer.
4. Positive urine drug screen for substances of abuse other than cannabis.
5. Heavy nicotine use (consumption of >40 cigarettes or >36 mg of nicotine from
other sources [e.g., vaping products] daily) or daily use of smokeless tobacco.
7. Subjects of reproductive potential who are (hetero) sexually active but unwilling to
use acceptable means of contraception through the EOS. For clarity, subjects who are
at least 1 year post-menopausal are not of reproductive potential. Acceptable means of
contraception include:
1. Subjects who have been surgically sterilized.
2. Females of reproductive potential: diaphragm, injectable, oral/patch
contraceptives for a minimum of 6 weeks, contraceptive sponge, implant, or
intrauterine device in use prior to enrollment.
3. Males: condom in combination with any of the above means of contraception.
4. All subjects: abstinence may be an acceptable means of contraception as long as
the individual consents to initiate immediate use of double barrier protection
for the duration of the study should (hetero) sexual intercourse occur.
8. Subjects who are nursing or who have positive or indeterminate pregnancy tests at
either Screening (serum test) or enrollment (urine test).
9. Use of any experimental agent within 1 month or 5 half-lives of Screening, whichever
is longer.
10. Subjects who are employees or immediate family members of employees of the site,
Sponsor or study-related vendors.
11. History of a serious allergic or hypersensitivity reaction to risperidone or LYN-005
excipients (refer to Investigator's Brochure).
12. Subjects with history of X-ray, computed tomography (CT) scan or angiogram of the
abdomen within one year of Screening.
13. Subjects with CYP2D6 poor or underdetermined metabolizer status based on genetic
testing.
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