Analgesic AllergyPhase 1NCT02775981
Pharmacokinetic Study of Intranasal RX0041-002 in Hepatic-Impaired Individuals and Subjects With Normal Hepatic Function
A Phase 1 study testing RX0041-002 in people with Analgesic Allergy, run by Pharmaceutical Project Solutions, Inc. at 1 site in United States.
Trial summary
The primary objective of this study is to evaluate the potential effect of hepatic impairment on the systemic pharmacokinetics of RX0041-002 following single dose intranasal administration. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Analgesic Allergy
- What is being tested?
- RX0041-002
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to Sep 2016
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female.
- Greater than or equal to 18 years of age and able to understand and comply with protocol requirements, provide written informed consent and HIPAA authorization; ± 10 years for individual age-matched controls.
- Females (if of child-bearing potential and sexually active) and males (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method from the first dose and for 8 days following administration of study drug. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm, intrauterine device (IUD), condom, surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method or withdrawal.
- BMI ≥ 18 ≤ 32 ; ± 20% for BMI-matched controls
- Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance.
- In general, good health aside from hepatic disease (for the hepatically impaired group only) and associated conditions as ascertained by physical examination (PE) including measurement of supine and standing vital signs, medical history, clinical laboratory evaluation, and 12-lead electrocardiogram (ECG).
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- Hepatic Subjects
- Hepatic-impaired subjects will be Class B or C according to Child-Pugh classification. The hepatic impairment will have been identified by a typical medical history, physical examination, coagulation tests and abnormal liver function tests (including bilirubin and albumin) at screening.
- Healthy Volunteers
- Volunteers will be healthy and age, BMI and gender-matched controls for the hepatic subjects.
Who cannot join
- A subject will be excluded from the study if he or she meets the following criteria:
- Less than 18 years of age.
- Has a known allergy to any ester based anesthetics including cocaine HCl, procaine, tetracaine, chloroprocaine, dibucaine, or benzocaine amide based anesthetic allergies are NOT exclusionary. Amide based anesthetics are : lidocaine, mepivicaine, bupivicaine, levobupivicaine, ropivicaine, etidocaine, prilocaine, and articaine.
- Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study.
- The use of amphetamines, methylphenidate or other stimulant prescription and nonprescription products such as pseudoephedrine, bronchial inhalers containing sympathomimetics (epinephrine or other beta-receptor agonist) or herbal products in the 7 days prior to screening or has a need to use these drugs during the course of the study.
- Use of any Seratonin uptake inhibitor/Serotonin-norepinephrine reuptake inhibitors, antidepressants or tricyclic antidepressant up to7 days or 5 half-lives (whichever is longer) prior to screening or has a need to use these drugs during the screening period and throughout the time period of the trial.
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- Use of Monoamine Oxidase Inhibitor drugs up to 14 days prior to screening or has a need to use these drugs during the screening period and throughout the time period of the trial.
- GI abnormalities
- History of hepatitis (for healthy control subjects only)
- Elevated aspartate aminotransferase/alanine aminotransferase /bilirubin (for healthy control subjects only),
- HIV
- Excessive use of alcohol/tobacco/caffeine.
- Has previously received study drug.
- Has a history of abuse of controlled substances, nasal or otherwise, or has damage to the nasal space, that in the opinion of the investigator might interfere with the ability to absorb RX0041-002.
- Has severely traumatized mucosa or sepsis in the nasal cavity.
- Has participated in an investigational study or received an investigational drug within 30 days preceding the randomization.
- Is a pregnant or nursing mother.
- Has a positive pregnancy test at Screening or Day -1.
- Has a history of seizure, with the exception of febrile seizures.
- Has symptomatic cardiovascular disease.
- Has a history of or currently suffers from hyperthyroidism.
- Has a known personal or family history of hereditary pseudocholinesterase deficiency. Study participants will be screened by asking about personal or family history of anesthetic reaction, anesthetic death, and previous diagnosis of psuedocholinesterase deficiency in a relative or personally. Subjects identified with pseudocholinesterase deficiency are at risk for delayed recovery with certain anesthetics (e.g. succinylcholine and ester-based anesthetics).
- Has a known personal or family history of pheochromocytoma. Study participants will be specifically asked if they have been treated for a pheochromocytoma previously or if they have a family member who has been diagnosed with pheochromocytoma (since 10% of these are familial).
- Has a known personal or family history of adrenal tumor.
- Clinically significant ECG abnormalities, based upon the impression of the investigator.
- Has a positive urine test result for drugs of abuse (amphetamines, barbiturates, cocaine metabolites, opiates and oxycodone) or cannabinoids at Screening or on Day 1; exception for hepatic subjects who may medically require one of the drugs for treatment (e.g., periodic opiates) and may, at the discretion of the investigator, be positive at screening, but must be negative at Day -1.
- Blood chemistry values judged clinically significant by the investigator. aa.Donation of blood (one pint or greater) within four weeks prior to administration of study medication.
- bb. Not suitable for entry into the study in the opinion of the investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
Comprehensive Clinical Researc
Berlin, New Jersey, 08009
About this study
Official title: A Phase-1 Study Comparing the Pharmacokinetics of Intranasal RX0041-002 in Hepatic-Impaired Individuals and Subjects With Normal Hepatic Function
The primary objective of this study is to evaluate the potential effect of hepatic impairment on the systemic pharmacokinetics of RX0041-002 following single dose intranasal administration. The secondary objective is to evaluate the safety and tolerability of intranasal RX0041-002 in subjects with normal hepatic function and hepatic impairment.
Read the detailed description
This is a Phase 1, single dose, open-label study comparing the plasma pharmacokinetics and safety of RX0041-002 between subjects with hepatic impairment and age/gender/BMI-matched subjects with normal hepatic function.
DOSAGE
All subjects will receive a single treatment consisting of four (4) ml of a 4% solution of RX0041-002 (corresponding to 160 mg cocaine HCl) applied for 20 minutes to both nostrils using cotton pledgets. RX0041-002 Topical Solution (4%) will be provided by the Sponsor, supplied in 4 mL bottles. RX0041-002 Topical Solution contains citric acid, D\&C Yellow No. 10, FD\&C Green No. 3, sodium benzoate, and water.
DURATION OF STUDY
Total duration of study participation for each subject will be approximately 23 days not counting the variable 30 days for adverse event follow-up and resolution, if required. During that time, subjects will be screened for a maximum of 21 days and then confined to the study unit for approximately 45 hours for Day -1 evaluations, dosing (Day 1), blood sampling and safety assessments (Day 1-2).
NUMBER OF SUBJECTS
A sufficient number of subjects will be enrolled to complete 12 subjects with hepatic impairment, male or female volunteers ≥ 18 years of age. An additional 12 healthy, non-hepatically impaired, male or female volunteers will be enrolled as the comparator group. These subjects will be approximately age, body mass index (BMI) \& gender-matched to the subjects with hepatic impairment. Hepatic impairment will be classified as moderate or severe and each grade/class will be defined according to Child-Pugh classification (Class B or C) . The liver impairment will be identified by a typical medical history, physical examination, coagulation and abnormal liver function tests (including bilirubin and albumin) at screening.
SAFETY PARAMETERS
Prior to enrollment (screening) and at the completion of the study, or at premature discontinuation, each subject will undergo a complete physical examination plus vital signs, clinical laboratory testing (serum chemistry, hematology, and urinalysis), and coagulation. In addition, subjects will be screened for inclusion with a 12-lead electrocardiogram, a urinary screen for drugs of abuse and blood tests for alcohol, serology tests for HIV antibody. Breath alcohol and urine drug screens will be repeated at check-in on Day -1 of the study. Females of child bearing potential will also be screened for inclusion with a serum pregnancy test. Urine pregnancy tests will also be performed at check-in on Day -1.
Each subject will be queried for the occurrence of adverse experiences following dosing and during blood sampling. Vital sign monitoring and recordings, will be obtained at baseline (pre-dose) (Day 1). Blood pressure, heart rate, respiratory rate and oral temperature will be taken and recorded every 15 minutes beginning immediately prior to dosing and for every 15 minutes for the first 60 minutes following pledget insertion. For the next 120 minutes (up to 180 minutes' post pledget insertion) vital sign recordings to include blood pressure, heart rate, respiratory rate and oral temperature measurements will be taken and recorded every 30 minutes to the 180 minute (3 Hour) post pledget insertion time point. Vital sign recordings to include blood pressure, heart rate, respiratory rate and oral temperature measurements will continue to be taken and recorded at hour 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32 hours from time of pledget insertion or if necessary until the patient is clinically stable.
A nasal exam will be conducted, visually, pre-dose (Day 1) and at the end of study (Day 2) to determine if irritation is present at the application site following drug administration.
PHARMACOKINETIC BLOOD SAMPLING AND ANALYSIS
Pharmacokinetic blood samples will be drawn at the following times relative to the initiation of RX0041-002 dosing.
Subjects will be dosed and blood pharmacokinetic sampling will be conducted at 0 hour (pre-dose), and post dose at: 7 minutes, 15 minutes, 20 minutes, (immediately after pledget removal) 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, and 2, 3, 4, 6, 8, 10, 12, 24, 28 and 32 hours, based upon the beginning of dose application. For each time point, a minimum of 8 ml of blood will be sampled.
Total concentrations of cocaine and it major metabolites will be determined in all samples.
- Conditions
- Analgesic Allergy
- Being tested
- RX0041-002
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RX0041-002Drug
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | RX0041-002 Receives: Drug: RX0041-002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Concentration (Cax)
Measured: 32 Hours
Area under the plasma concentration versus time curve (AUC)
Measured: 32 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2016 (estimated)
- Study startFeb 2016
- Primary completionJul 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Analgesic AllergyStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmaceutical Project Solutions, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cognitive Research Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02775981
- Sponsor's protocol ID
- CTS2015014
- Status last verified
- Sep 2018
- First submitted
- 23 Mar 2016
- Last updated
- 6 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase-1 Study Comparing the Pharmacokinetics of Intranasal RX0041-002 in Hepatic-Impaired Individuals and Subjects With Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT02775981
- Acronym / sponsor ID
- CTS2015014
- Conditions
- Analgesic Allergy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Pharmaceutical Project Solutions, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Cognitive Research Corporation
- Study start
- Feb 2016
- Primary completion
- Jul 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 18 May 2016 (estimated)
- 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.
The primary objective of this study is to evaluate the potential effect of hepatic impairment on the systemic pharmacokinetics of RX0041-002 following single dose intranasal administration. The secondary objective is to evaluate the safety and tolerability of intranasal RX0041-002 in subjects with normal hepatic function and hepatic impairment.
Detailed description
This is a Phase 1, single dose, open-label study comparing the plasma pharmacokinetics and safety of RX0041-002 between subjects with hepatic impairment and age/gender/BMI-matched subjects with normal hepatic function.
DOSAGE
All subjects will receive a single treatment consisting of four (4) ml of a 4% solution of RX0041-002 (corresponding to 160 mg cocaine HCl) applied for 20 minutes to both nostrils using cotton pledgets. RX0041-002 Topical Solution (4%) will be provided by the Sponsor, supplied in 4 mL bottles. RX0041-002 Topical Solution contains citric acid, D\&C Yellow No. 10, FD\&C Green No. 3, sodium benzoate, and water.
DURATION OF STUDY
Total duration of study participation for each subject will be approximately 23 days not counting the variable 30 days for adverse event follow-up and resolution, if required. During that time, subjects will be screened for a maximum of 21 days and then confined to the study unit for approximately 45 hours for Day -1 evaluations, dosing (Day 1), blood sampling and safety assessments (Day 1-2).
NUMBER OF SUBJECTS
A sufficient number of subjects will be enrolled to complete 12 subjects with hepatic impairment, male or female volunteers ≥ 18 years of age. An additional 12 healthy, non-hepatically impaired, male or female volunteers will be enrolled as the comparator group. These subjects will be approximately age, body mass index (BMI) \& gender-matched to the subjects with hepatic impairment. Hepatic impairment will be classified as moderate or severe and each grade/class will be defined according to Child-Pugh classification (Class B or C) . The liver impairment will be identified by a typical medical history, physical examination, coagulation and abnormal liver function tests (including bilirubin and albumin) at screening.
SAFETY PARAMETERS
Prior to enrollment (screening) and at the completion of the study, or at premature discontinuation, each subject will undergo a complete physical examination plus vital signs, clinical laboratory testing (serum chemistry, hematology, and urinalysis), and coagulation. In addition, subjects will be screened for inclusion with a 12-lead electrocardiogram, a urinary screen for drugs of abuse and blood tests for alcohol, serology tests for HIV antibody. Breath alcohol and urine drug screens will be repeated at check-in on Day -1 of the study. Females of child bearing potential will also be screened for inclusion with a serum pregnancy test. Urine pregnancy tests will also be performed at check-in on Day -1.
Each subject will be queried for the occurrence of adverse experiences following dosing and during blood sampling. Vital sign monitoring and recordings, will be obtained at baseline (pre-dose) (Day 1). Blood pressure, heart rate, respiratory rate and oral temperature will be taken and recorded every 15 minutes beginning immediately prior to dosing and for every 15 minutes for the first 60 minutes following pledget insertion. For the next 120 minutes (up to 180 minutes' post pledget insertion) vital sign recordings to include blood pressure, heart rate, respiratory rate and oral temperature measurements will be taken and recorded every 30 minutes to the 180 minute (3 Hour) post pledget insertion time point. Vital sign recordings to include blood pressure, heart rate, respiratory rate and oral temperature measurements will continue to be taken and recorded at hour 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32 hours from time of pledget insertion or if necessary until the patient is clinically stable.
A nasal exam will be conducted, visually, pre-dose (Day 1) and at the end of study (Day 2) to determine if irritation is present at the application site following drug administration.
PHARMACOKINETIC BLOOD SAMPLING AND ANALYSIS
Pharmacokinetic blood samples will be drawn at the following times relative to the initiation of RX0041-002 dosing.
Subjects will be dosed and blood pharmacokinetic sampling will be conducted at 0 hour (pre-dose), and post dose at: 7 minutes, 15 minutes, 20 minutes, (immediately after pledget removal) 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, and 2, 3, 4, 6, 8, 10, 12, 24, 28 and 32 hours, based upon the beginning of dose application. For each time point, a minimum of 8 ml of blood will be sampled.
Total concentrations of cocaine and it major metabolites will be determined in all samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: RX0041-002RX0041-002 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female.
- Greater than or equal to 18 years of age and able to understand and comply with protocol requirements, provide written informed consent and HIPAA authorization; ± 10 years for individual age-matched controls.
- Females (if of child-bearing potential and sexually active) and males (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method from the first dose and for 8 days following administration of study drug. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm, intrauterine device (IUD), condom, surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method or withdrawal.
- BMI ≥ 18 ≤ 32 ; ± 20% for BMI-matched controls
- Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance.
Key exclusion criteria (28 listed)
- Less than 18 years of age.
- Has a known allergy to any ester based anesthetics including cocaine HCl, procaine, tetracaine, chloroprocaine, dibucaine, or benzocaine amide based anesthetic allergies are NOT exclusionary. Amide based anesthetics are : lidocaine, mepivicaine, bupivicaine, levobupivicaine, ropivicaine, etidocaine, prilocaine, and articaine.
- Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study.
- The use of amphetamines, methylphenidate or other stimulant prescription and nonprescription products such as pseudoephedrine, bronchial inhalers containing sympathomimetics (epinephrine or other beta-receptor agonist) or herbal products in the 7 days prior to screening or has a need to use these drugs during the course of the study.
- Use of any Seratonin uptake inhibitor/Serotonin-norepinephrine reuptake inhibitors, antidepressants or tricyclic antidepressant up to7 days or 5 half-lives (whichever is longer) prior to screening or has a need to use these drugs during the screening period and throughout the time period of the trial.
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 |
|---|---|---|
| RX0041-002 | Drug | Active |
Primary outcome
Peak Plasma Concentration (Cax)
Time frame: 32 Hours
Area under the plasma concentration versus time curve (AUC)
Time frame: 32 Hours
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 6 Sep 2018.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 RX0041-002 in people with Analgesic Allergy, run by Pharmaceutical Project Solutions, Inc. 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 10 inclusion and 28 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 6 Sep 2018. 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?
Peak Plasma Concentration (Cax) (time frame: 32 Hours). The study lists 2 primary outcomes in all. 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 6 Sep 2018.