Safety and Pharmacokinetics of Intravenous BaclofenPhase 1NCT01931319
Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
A Phase 1 study testing Intravenous baclofen in people with Safety and Pharmacokinetics of Intravenous Baclofen, run by University of Minnesota at 1 site in United States.
Trial summary
The objective of this study is to determine safety and characterize pharmacokinetics of higher doses of intravenous baclofen in healthy subjects. Thirty-six healthy adults received a single dose of PO baclofen (10mg, 15mg or 20mg) and a 10-minute infusion of IV baclofen (7.5mg, 11.5mg or 15mg respectively) with a… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety and Pharmacokinetics of Intravenous Baclofen
- What is being tested?
- Intravenous baclofen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jun 2014
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and females between the ages of 18-65.
- Subjects are capable of giving informed consent.
- Female subjects must be post-menopausal for at least 1 year, or surgically incapable of bearing children, or practicing at least one or more of the following methods of contraception for three months prior to, and during the study: hormonal, intrauterine device (IUD), or barrier method in combination with a spermicide.
- Subject should be medication free, other than hormonal birth control, for 48 hours before through 24 hours after study drug administration. If the need for medication is identified during this time period, it will be discussed with and approved by the PI.
Who cannot join
- Women who are pregnant.
- Women who are breastfeeding.
- Subject has a history of intolerance to IV administration of medication.
- Subject has a known hypersensitivity to baclofen.
- Subject has a significant history of cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal or hepatic disease
- Subject has taken or used any investigational drug or device in the 30 days prior to screening.
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- Subject has taken either prescribed or over the counter medication for 48 hours prior to baclofen administration on either of the study days, other than hormonal birth control.
- Subject reveals clinically significant abnormalities on screening laboratory tests.
- Subject is a non-English speaker, such that ability to ascertain neurological status would require an interpreter.
- Sleep deprivation (for example. working the night shift the evening prior to the study).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Prevention of Baclofen Withdrawal Syndrome: Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
The objective of this study is to determine safety and characterize pharmacokinetics of higher doses of intravenous baclofen in healthy subjects.
Thirty-six healthy adults received a single dose of PO baclofen (10mg, 15mg or 20mg) and a 10-minute infusion of IV baclofen (7.5mg, 11.5mg or 15mg respectively) with a minimum 48-hour wash out period. Twelve subjects also received a 60-minute infusion of 15mg IV baclofen following an additional 48-hour wash out period.
The pharmacokinetic and tolerability information gained from this study will support the development of further studies to assess the use of IV baclofen to prevent or treat baclofen withdrawal syndrome.
Read the detailed description
This randomized, open-label, dose escalation, crossover study was conducted at a contract clinical research facility. Three single doses were evaluated using three cohorts (N=12 per cohort). Study doses were as follows: cohort 1 - 7.5mg IV and 10mg PO, cohort 2 - 11.5mg IV and 15mg PO, and cohort 3 - 15mg IV and 20mg PO. The IV baclofen doses for this trial were based on a 75% bioavailability observed in a previous low dose study.16 The oral formulation of the study drug used in this trial was 10mg baclofen tablet (Teva Pharmaceutical Industries Ltd.) and is commercially available. The intravenous formulation was 2mg/mL solution manufactured by Aptuit LLC. for this study. IV infusions were administered over 10 minutes. In addition, cohort 3 received 15mg over a 60-minute infusion. There was a minimum 48-hour washout period between doses. Initially, 3 subjects received study drug at a given dose, after assessing the safety and tolerance of baclofen the additional 9 subjects received study drug.
- Being tested
- Intravenous baclofen
- Keywords
- baclofen withdrawal, interruption, spasticity, pharmacokinetics, tolerability, intravenous
- Medical subject headings
- Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous baclofenDrug
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Baclofen | Experimental | Three single doses were evaluated using three cohorts (N=12 per cohort). Subjects received single doses of baclofen: 7.5, 11.5 or 15mg 10-minute intravenous infusion administered over 10 minutes by an infusion pump and 10, 15, or 20mg taken orally with a 48-hour washout phase between oral and intravenous arms of the study. Initially, 3 subjects received study drug at a given dose, after assessing the safety and tolerance of baclofen the additional 9 subjects received study drug. Receives: Drug: Intravenous baclofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessments
Blood Pressure \& Pulse: Recorded every 5 minutes immediately prior to, and during the IV infusion, then every 15 minutes for 1 hour, then every hour for 12 hours.
Assessment of sedation / sleepiness: Subjects will be assessed by using the sleepiness scale prior to drug administration then every 30 minutes for four hours after drug administration.
Ataxia and nystagmus: Measured using the following rating scale and definitions of ataxia and nystagmus.
0=none, 1=mild, 2=severe
Ataxia: For those who are ambulatory, this will be assessed by gait. Ratings will be:
mild-unsteady with tandem gait testing, but able to perform without assistance severe-unable to perform gait testing without assistance. For non-ambulatory subjects, ataxia will be assessed by finger to nose and finger pursuit maneuvers.
Nystagmus:
mild-present on extreme gaze; severe-present on midline gaze
Measured: Upto 24 hours following drug administration
Secondary outcomes (3)
Maximum Concentration(Cmax)
Cmax: Cmax is the maximum baclofen concentration observed
Measured: Upto 24 hours following drug administration
AUC(0-inf)
AUC(0-inf): Area under the plasma concentration-versus-time curve from time zero to infinity
Measured: Upto 24 hours after drug administration
Plasma Decay Half-life (T1/2)
Plasma Decay Half-life(T1/2): Plasma decay half-life is the time measured for the plasma concentration to decrease by one half
Measured: Up to 24 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2013 (estimated)
- Study startJan 2014
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Safety and Pharmacokinetics of Intravenous BaclofenStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- 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
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Paralyzed Veterans of America Research Foundation
- Responsible party
- Sponsor
- Investigators
- Robert L Kriel, MD, Principal investigator, University of MinnesotaJames C Cloyd, PharmD, Principal investigator, University of MinnesotaLinda E Krach, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01931319
- Sponsor's protocol ID
- Baclofen_Dose escalation
- Status last verified
- May 2019
- First submitted
- 14 Aug 2013
- Last updated
- 7 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Baclofen Withdrawal Syndrome: Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT01931319
- Acronym / sponsor ID
- Baclofen_Dose escalation
- Keywords
- baclofen withdrawal, interruption, spasticity, pharmacokinetics, tolerability, intravenous
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Paralyzed Veterans of America Research Foundation
- Study start
- Jan 2014
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 29 Aug 2013 (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 objective of this study is to determine safety and characterize pharmacokinetics of higher doses of intravenous baclofen in healthy subjects.
Thirty-six healthy adults received a single dose of PO baclofen (10mg, 15mg or 20mg) and a 10-minute infusion of IV baclofen (7.5mg, 11.5mg or 15mg respectively) with a minimum 48-hour wash out period. Twelve subjects also received a 60-minute infusion of 15mg IV baclofen following an additional 48-hour wash out period.
The pharmacokinetic and tolerability information gained from this study will support the development of further studies to assess the use of IV baclofen to prevent or treat baclofen withdrawal syndrome.
Detailed description
This randomized, open-label, dose escalation, crossover study was conducted at a contract clinical research facility. Three single doses were evaluated using three cohorts (N=12 per cohort). Study doses were as follows: cohort 1 - 7.5mg IV and 10mg PO, cohort 2 - 11.5mg IV and 15mg PO, and cohort 3 - 15mg IV and 20mg PO. The IV baclofen doses for this trial were based on a 75% bioavailability observed in a previous low dose study.16 The oral formulation of the study drug used in this trial was 10mg baclofen tablet (Teva Pharmaceutical Industries Ltd.) and is commercially available. The intravenous formulation was 2mg/mL solution manufactured by Aptuit LLC. for this study. IV infusions were administered over 10 minutes. In addition, cohort 3 received 15mg over a 60-minute infusion. There was a minimum 48-hour washout period between doses. Initially, 3 subjects received study drug at a given dose, after assessing the safety and tolerance of baclofen the additional 9 subjects received study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous Baclofen | Experimental | Drug: Intravenous baclofenThree single doses were evaluated using three cohorts (N=12 per cohort). Subjects received single doses of baclofen: 7.5, 11.5 or 15mg 10-minute intravenous infusion administered over 10 minutes by an infusion pump and 10, 15, or 20mg taken orally with a 48-hour washout phase between oral and intravenous arms of the study. Initially, 3 subjects received study drug at a given dose, after assessing the safety and tolerance of baclofen the additional 9 subjects received study drug. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females between the ages of 18-65.
- Subjects are capable of giving informed consent.
- Female subjects must be post-menopausal for at least 1 year, or surgically incapable of bearing children, or practicing at least one or more of the following methods of contraception for three months prior to, and during the study: hormonal, intrauterine device (IUD), or barrier method in combination with a spermicide.
- Subject should be medication free, other than hormonal birth control, for 48 hours before through 24 hours after study drug administration. If the need for medication is identified during this time period, it will be discussed with and approved by the PI.
Key exclusion criteria (10 listed)
- Women who are pregnant.
- Women who are breastfeeding.
- Subject has a history of intolerance to IV administration of medication.
- Subject has a known hypersensitivity to baclofen.
- Subject has a significant history of cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal or hepatic disease
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 |
|---|---|---|
| Intravenous baclofen | Drug | Intravenous Baclofen |
Primary outcome
Safety assessments
Time frame: Upto 24 hours following drug administration
Blood Pressure \& Pulse: Recorded every 5 minutes immediately prior to, and during the IV infusion, then every 15 minutes for 1 hour, then every hour for 12 hours. Assessment of sedation / sleepiness: Subjects will be assessed by using the sleepiness scale prior to drug administration then every 30 minutes for four hours after drug administration. Ataxia and nystagmus: Measured using the following rating scale and definitions of ataxia and nystagmus. 0=none, 1=mild, 2=severe Ataxia: For those who are ambulatory, this will be assessed by gait. Ratings will be: mild-unsteady with tandem gait testing, but able to perform without assistance severe-unable to perform gait testing without assistance. For non-ambulatory subjects, ataxia will be assessed by finger to nose and finger pursuit maneuvers. Nystagmus: mild-present on extreme gaze; severe-present on midline gaze
3 secondary outcomes
Maximum Concentration(Cmax)
Time frame: Upto 24 hours following drug administration
AUC(0-inf)
Time frame: Upto 24 hours after drug administration
Plasma Decay Half-life (T1/2)
Time frame: Up to 24 hours after drug administration
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 7 May 2019.
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.
Robert L Kriel, MD principal investigator
University of Minnesota
James C Cloyd, PharmD principal investigator
University of Minnesota
Linda E Krach, MD principal investigator
University of Minnesota
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 Intravenous baclofen in people with Safety and Pharmacokinetics of Intravenous Baclofen, run by University of Minnesota 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 4 inclusion and 10 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 7 May 2019. 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?
Safety assessments (time frame: Upto 24 hours following drug administration). 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 7 May 2019.