Fluphenazine

Associated long-acting platforms

Oil depot

Administration route

Intramuscular, Subcutaneous

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Prolixin is commercially manufactured by Bristol-Myers Squibb at 125-199.64 USD per 5 mL vial.

Tentative equipment list for manufacturing

• Jacketed stirred tank reactors • Pipeline/feed pumps • Circulation pump • Gas-liquid separators • Distillation • Mixing vessels and filtration system

Manufacturing

Compliant with aseptic conditions of GMP: • Active Ester synthesis using decanoic acid and dehydrating agents • Scale up in controlled reaction conditions • Depot formulation preparation—oil-based injectable depot prepared using sesame oil and benzyl alcohol, PEG 300/400, solubilizers, and poloxamer surfactants (poloxamer 407/188).

Specific analytical instrument required for characterization of formulation

• High-Performance Liquid Chromatography (HPLC UV/DAD/PDA) • Liquid Chromatography–Mass Spectrometry (LC–MS/MS) • Gas Chromatography–Mass Spectrometry (GC–MS) • Differential Scanning Calorimetry (DSC)

FP-CL1

Identifier

NCT00356200

Link

https://clinicaltrials.gov/study/NCT00356200

Phase

Phase II

Status

Terminated

Sponsor

Tufts Medical Center

More details

We are doing this research study to evaluate the effectiveness and safety of fluphenazine decanoate when injected with a needle into psoriasis lesions in adults. Fluphenazine decanoate is FDA (U.S. Food and Drug Administration) approved for use in people who have schizophrenia and psychotic symptoms. Fluphenazine decanoate is not approved by the FDA for use in psoriasis. Fluphenazine decanoate slows T cell growth in cells in laboratory test tubes. Its usefulness and safety in people with psoriasis will be investigated in this study.

Purpose

Fluphenazine Decanoate for Psoriasis

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2006-07-01

Anticipated Date of Last Follow-up
2010-12-20

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2007-12-01

Actual Completion Date
2008-09-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Adults 18 to 65 years of age with psoriasis, in general good health * Must have symmetric target lesions approximately 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline target lesion score of 6 or higher (scale of 0-12) for each target * Women of childbearing potential must agree to use two forms of contraception for the duration of the study Exclusion Criteria: * Infliximab (Remicade) or alefacept (Amevive) within the past 6 months (24 weeks) * Etanercept (Enbrel), efalizumab (Raptiva), adalimumab (Humira), or other tumor necrosis factor- (TNF)-alpha inhibitor within the past 3 months (12 weeks) * Other systemic psoriasis therapies (e.g., methotrexate, cyclosporine, acitretin) or PUVA (psoralen plus ultraviolet A) within the past 4 weeks * U

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

10

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

GAP

Identifier

NCT02374567

Link

https://clinicaltrials.gov/study/NCT02374567

Phase

Phase III

Status

Terminated

Sponsor

Hannover Medical School

More details

The purpose of this multicenter-study is to investigate safety of psychopharmacological treatment and rates of adverse drug reactions in gerontopsychiatric inpatients. Elderly people are at higher risk for developing side effects under pharmacological treatment due to an altered metabolic situation, higher comorbidity rates and often polypharmacy. Furthermore gerontopsychiatric patients can often not articulate their symptoms clearly, for example due to pronounced cognitive impairment. The aim of the study is to gain valid data of possible adverse drug reaction rates, their potential risk factors and outcome, as well as medical prescription practises. To assess these outcomes an intensive pharmacovigilance-monitoring will be conducted at the five participating study sites. At Baseline d

Purpose

Pharmacovigilance in Gerontopsychiatric Patients

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-01-01

Anticipated Date of Last Follow-up
2018-02-27

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2017-06-28

Actual Completion Date
2017-06-28

Studied populations

Age Cohort

• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Age 65+ years old * Inpatients treated at one of the geriatric psychiatry study sites. * Signed consent form ( Patient and/or legally authorized custodian) Exclusion Criteria: * Patients that are incapable to give their informed consent and are not under legally authorized custodianship. * Parallel participation in another clinical trial.

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

407

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Not provided

Studied LA-formulation(s)

Studied route(s) of administration

Not provided

Use case

Treatment

Key resources

N01 MH090001-06

Identifier

NCT00014001

Link

https://clinicaltrials.gov/study/NCT00014001

Phase

Marketed

Status

Completed

Sponsor

National Institute of Mental Health (NIMH)

More details

Not provided

Purpose

CATIE- Schizophrenia Trial

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2000-12-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Unspecified

Comments about the studied populations

Not provided

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

1600

Allocation

Randomized

Intervention model

Cross-over assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Not provided

Studied LA-formulation(s)

Studied route(s) of administration

Not provided

Use case

Treatment

Key resources

LAMP

Identifier

NCT05766007

Link

https://clinicaltrials.gov/study/NCT05766007

Phase

Not provided

Status

Recruiting

Sponsor

University of Liverpool

More details

The goal of this observational study is to learn about how long-acting injectable antipsychotic (LAIA) medications are affected by the changes that take place in the body during pregnancy, and how much an unborn baby is exposed to. The investigators are also interested in the amount of these drugs that enters into breastmilk and taken by babies during breastfeeding. In addition to their regular clinic visits to receive long-acting mental health medicine injection, participants will be invited for up to four study visits between day 2 and 14 after the injection. This will happen only once during pregnancy, and once during the breastfeeding period to collect a few drops of blood on special filter paper card from the finger using safety lancet. A few drops of breastmilk will also be collecte

Purpose

Long-acting Injectable Antipsychotics for Mental Ill-Health in Pregnancy and Postpartum

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-08-01

Anticipated Date of Last Follow-up
2025-02-25

Estimated Primary Completion Date
2025-12-31

Estimated Completion Date
2026-06-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• Female

Accepts pregnant individuals
Yes

Accepts lactating individuals
Yes

Accepts healthy individuals
Yes

Comments about the studied populations

Not provided

Health status

Not provided

Study type

Not provided

Enrollment

125

Allocation

Not provided

Intervention model

Not provided

Intervention model description

Not provided

Masking

Not provided

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Not provided

Use case

Treatment

Key resources

FP-CL2

Identifier

NCT00929578

Link

https://clinicaltrials.gov/study/NCT00929578

Phase

Phase II

Status

Completed

Sponsor

Tufts Medical Center

More details

The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine in adult subjects with psoriasis.

Purpose

Fluphenazine Hydrochloride for Psoriasis

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2008-11-01

Anticipated Date of Last Follow-up
2017-03-02

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2010-11-01

Actual Completion Date
2011-01-01

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Adults 18 to 65 years of age with psoriasis, in general good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination * Must have symmetric target lesions 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline Target Lesion Score (TLS) of 6 or higher (scale of 0-12) for each target * Women are eligible to participate in the study if they meet one of the following criteria: * Women who are postmenopausal (for at least one year), sterile, or hysterectomized * Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout the study and for 60 days after the last dose of

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

15

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Triple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Benzyl alcohol and poloxamer 407/188

Residual solvents used

No residual solvent used

Description

Fluphenazine compound

Brief description

This invention relates to new 10-(piperazinylalkyl) perfluoroalkylphenothiazine derivatives The novel compounds of this invention are of value as therapeutic agents. More specifically, the compounds of this invention have utility as antiemetics, tranquilizers, antihistaminics, spasmolytics, antishock agents and potentiators of various drugs such as analgetics and anesthetics When used as tranquilizers, these compounds have the ability to abate mental disturbances such as anxiety, confusion or excitation without physical incapacitation In addition, these compounds have chemotherapeutic or antimicrobial activity, such as antibacterial and fungicidal activity Further, the novel compounds of this invention have a surprisingly low degree of toxicity.

Representative patent

US3058979

Category

Compound

Patent holder

SMITH KLINE FRENCH LAB

Exclusivity

Not provided

Expiration date

May 13, 1977

Status

Expired (US, GB)

Publications

Fluphenazine decanoate (depot) and enanthate for schizophrenia.

Maayan N — Cochrane Database Systematic Review — 2015-02-05

Summary: There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.

Background: Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects.

Objectives: To assess the effects of fluphenazine decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes.

Search methods: We searched the Cochrane Schizophrenia Group's Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials.

Selection criteria: We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations.

Data collection and analysis: We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table.

Main results: This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low.Compared with placebo, use of fluphenazine decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine decanoate with placebo reported clinically significant changes in global state or hospital admissions.Fluphenazine decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine decanoate with oral neuroleptics reported death or hospital admissions.No significant difference in relapse rates in the medium term between fluphenazine decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine decanoate and fluphenazine enanthate. No study comparing fluphenazine decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions.

Authors' conclusions: There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.

A double-blind dose-reduction trial of fluphenazine decanoate for chronic, unstable schizophrenic patients.

Inderbitzin, L. B. — The American journal of psychiatry — 1994-01-01

Objective: This study evaluated the feasibility and impact of gradually reducing relatively high doses of fluphenazine decanoate by one-half for chronically impaired, poor inner-city patients with schizophrenia.

Method: Forty-three patients currently receiving an average of 23 mg (0.3 mg/kg) of fluphenazine decanoate every 2 weeks were divided alternately into a group to remain at current doses (control group) and a group to undergo stepwise 50% dose reduction over 5 months under double-blind conditions. Clinical status and side effects were assessed quarterly for a year. Relapse was determined clinically and by changes in psychopathology ratings.

Results: Eighty-six percent (N = 37) of the patients (control group, N = 17; reduced-dose group, N = 20) completed the study. The groups did not differ at baseline in demographic or clinical variables or neuroleptic dose. In the reduced-dose group, doses were lowered to an average of 11.5 mg every 2 weeks. The two groups did not differ throughout the year in number of relapses, and hospitalization rates fell similarly in both (overall, by about 67%). Clinical measures changed little. Extrapyramidal symptoms worsened in the control group but improved slightly in the reduced-dose group. Tardive dyskinesia worsened in both groups, but less in the reduced-dose group.

Conclusions: Maintenance neuroleptic doses much lower than the conventional ones can be achieved safely in schizophrenic patients by gradual reduction, without clinical worsening and perhaps with fewer extrapyramidal symptoms and less tardive dyskinesia. The two-thirds lower hospitalization rate, with substantial financial savings, apparently was due to nonspecific effects of research intervention.

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