Trial Outcomes & Findings for Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder (NCT NCT00130923)

Last Updated: 2019-05-09

Results Overview

Frequency of heavy drinking days is obtained each week retrospectively as the number of heavy drinking days during the prior week (assessed by the Timeline Followback Scale). A heavy drinking day is defined as 4 or more drinks per day for a female and 5 or more drinks per day for a male. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

95 participants

Primary outcome timeframe

6 months

Results posted on

2019-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Risperidone Long Acting Injectable (LAI) Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperdal Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Overall Study STARTED	49	46
Overall Study COMPLETED	36	32
Overall Study NOT COMPLETED	13	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.	Total n=95 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants	46 Participants n=7 Participants	95 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	41.7 years STANDARD_DEVIATION 10.1 • n=5 Participants	41.7 years STANDARD_DEVIATION 11.5 • n=7 Participants	41.70 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Region of Enrollment United States	49 Participants n=5 Participants	46 Participants n=7 Participants	95 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Change Over Time in Frequency of Heavy Drinking Days (Used to Evaluate Treatment Efficacy)	-.11 heavy drinking days per week Interval -1.12 to 0.9	.68 heavy drinking days per week Interval 0.083 to 1.28

SECONDARY outcome

Timeframe: 6 months

Frequency of drinking days is obtained each week retrospectively as the number of drinking days during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Average Over Time of Frequency of Drinking Days (Used to Evaluate Treatment Efficacy)	2.84 drinking days per week Interval 1.72 to 3.95	3.46 drinking days per week Interval 2.5 to 4.42

SECONDARY outcome

Timeframe: 6 months

A rater assesses the severity of illness and global impression using a scale from 1 to 7 (Clinical Global Impression), where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Average Over Time of Severity of Illness and Global Improvement (Used to Evaluate Treatment Efficacy)	4.02 ordinal unit of severity Interval 3.13 to 4.91	3.96 ordinal unit of severity Interval 3.08 to 4.83

SECONDARY outcome

Timeframe: 6 months

A rater assesses positive and negative symptoms of schizophrenia using a 30-item scale (Positive and Negative Symptom Score) Scores range from 30 to 210, where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Average Over Time of Positive and Negative Symptoms (Used to Evaluate Treatment Efficacy)	78.2 ordinal severity of symptoms Interval 64.9 to 91.5	75.5 ordinal severity of symptoms Interval 65.3 to 89.7

SECONDARY outcome

Timeframe: 6 months

A rater assesses social, occupational and psychological functioning on a hypothetical continuum of mental health - illness (using Global Assessment of Functioning); scores range from 100 to 1, where higher values represent a better outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Average Over Time of Global Functioning (Used to Evaluate Treatment Efficacy)	50.8 ordinal severity of impairment Interval 42.7 to 58.9	49.9 ordinal severity of impairment Interval 42.2 to 57.6

SECONDARY outcome

Timeframe: 6 months

Number of participants with medication adherence (defined as taking medication at least 75% of the days in the treatment period).

Outcome measures

Outcome measures
Measure	Risperidone Long Acting Injectable (LAI) n=49 Participants Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 Participants Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Number of Participants With Medication Adherence	43 Participants	28 Participants

Adverse Events

Risperidone Long Acting Injectable (LAI)

Serious events: 16 serious events

Other events: 27 other events

Deaths: 0 deaths

Oral Risperidone Aka Risperal

Serious events: 12 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Risperidone Long Acting Injectable (LAI) n=49 participants at risk Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 participants at risk Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Cardiac disorders Acute Coronary Syndrome	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Psychiatric disorders Agitation	2.0% 1/49 • Number of events 1 • 6 months	2.2% 1/46 • Number of events 4 • 6 months
Psychiatric disorders Anxiety	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Psychiatric disorders Delerium	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Psychiatric disorders Depression	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
General disorders Edema	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Epitaxis	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Injury, poisoning and procedural complications Fall	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
General disorders Fever	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Injury, poisoning and procedural complications Hip fracture	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Vascular disorders Hypertension	2.0% 1/49 • Number of events 2 • 6 months	0.00% 0/46 • 6 months
Injury, poisoning and procedural complications Injury, poisongin and procedural complications - Other, specify - Gunshot wound	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify Laceration	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify Accidental overdose	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Psychiatric disorders Psychiatric Disorders - Other, specify - unspecified	2.0% 1/49 • Number of events 1 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Psychiatric disorders Psychiatric Disorders - Other, specify Substance Dependence	4.1% 2/49 • Number of events 2 • 6 months	2.2% 1/46 • Number of events 8 • 6 months
Psychiatric disorders Psychosis	4.1% 2/49 • Number of events 2 • 6 months	10.9% 5/46 • Number of events 6 • 6 months
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/49 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Nervous system disorders Somnolence	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months
Psychiatric disorders Suicidal Ideation	4.1% 2/49 • Number of events 2 • 6 months	4.3% 2/46 • Number of events 5 • 6 months
Psychiatric disorders Suicide Attempt	2.0% 1/49 • Number of events 1 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify Colon Cancer	2.0% 1/49 • Number of events 1 • 6 months	0.00% 0/46 • 6 months

Other adverse events

Other adverse events
Measure	Risperidone Long Acting Injectable (LAI) n=49 participants at risk Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone Aka Risperal n=46 participants at risk Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Psychiatric disorders Anxiety	8.2% 4/49 • Number of events 4 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Psychiatric disorders Depression	8.2% 4/49 • Number of events 6 • 6 months	4.3% 2/46 • Number of events 3 • 6 months
Gastrointestinal disorders Diarrhea	8.2% 4/49 • Number of events 6 • 6 months	4.3% 2/46 • Number of events 2 • 6 months
Reproductive system and breast disorders Erectile Disfunction	6.1% 3/49 • Number of events 3 • 6 months	2.2% 1/46 • Number of events 1 • 6 months
Gastrointestinal disorders Gastrointestinal Disorder - Other, Hypersalivation	6.1% 3/49 • Number of events 4 • 6 months	0.00% 0/46 • 6 months
General disorders Injection Site Reactions	6.1% 3/49 • Number of events 15 • 6 months	0.00% 0/46 • 6 months
Psychiatric disorders Insomnia	10.2% 5/49 • Number of events 8 • 6 months	6.5% 3/46 • Number of events 3 • 6 months
Musculoskeletal and connective tissue disorders Musculo-Skeletal Connective Tissue Disorder-Other, Muscle Stiffness	8.2% 4/49 • Number of events 6 • 6 months	0.00% 0/46 • 6 months
General disorders Pain	10.2% 5/49 • Number of events 5 • 6 months	0.00% 0/46 • 6 months
Psychiatric disorders Psychiatric Disorders - Other, Specify: Substance Dependence	2.0% 1/49 • Number of events 2 • 6 months	6.5% 3/46 • Number of events 5 • 6 months
Nervous system disorders Somnolence	8.2% 4/49 • Number of events 7 • 6 months	4.3% 2/46 • Number of events 2 • 6 months
Gastrointestinal disorders Vomiting	10.2% 5/49 • Number of events 6 • 6 months	2.2% 1/46 • Number of events 1 • 6 months

Additional Information

Dr. Mary Brunette

Psychopharmacology Research Group

Phone: 603-271-5747

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place