Shock,HemorrhagicPhase 1NCT01951560
A Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1)
A Phase 1 study testing Valproic Acid and Isotonic saline solution in people with Shock,Hemorrhagic, run by Dr. Hasan Alam at 1 site in United States.
Trial summary
The purpose of the first part of this study is to determine the safety and tolerability of ascending doses of valproic acid (also known as Depacon) administered as intravenous infusion (IV) in doses ranging from 15 mg/kg to 250 mg/kg in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Shock,Hemorrhagic
- What is being tested?
- Valproic Acid and Isotonic saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to May 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female volunteers between the ages of 18 and 65 years, inclusive, in good health based on medical history, physical examination, ECG, and routine laboratory tests (blood chemistry, hematology, urinalysis, and drug screen).
- Female subjects must be surgically sterilized or postmenopausal. Criteria for menopause are surgical menopause (hysterectomy, oophorectomy) or age > 45 years with absence of menses for greater than 12 months or a serum follicle stimulating hormone (FSH) elevation > 25m IU/mL.(mIU/mL is the unit used to measure human chorionic gonadotropin (hCG) in pregnancy test). Tubal ligation with menses within the past 12 months is not considered to be surgical sterilization.
- Negative urine pregnancy test in female volunteers
- Body mass index (BMI) between 18 kg/m2 and 30 kg/m2
- Subjects must be non-smokers
- Negative alcohol screen
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- Willing and able to be confined to the clinical research facility as required by the protocol.
- Willing and able to comply with the investigational nature of the study and able to communicate well with investigators.
- Ability to comprehend and willingness to provide written informed consent in accordance with institutional and regulatory guidelines.
Who cannot join
- Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies; however, subjects with untreated, asymptomatic, seasonal allergies may be enrolled).
- Subjects with a-amylase >130 U/L or lipase >300 U/L or creatinine > upper limit of normal (ULN)
- Subjects with >2times ULN aspartate aminotransferase (AST) or alanine amino transferase (ALT) or >1.5 times total bilirubin
- Subjects whose screening ECG demonstrates at least one of the following: heart rate > 100 bpm for more than 30 minutes, (the combination of three of the graphical deflections seen on a typical ECG is called the(QRS)) > 120 msec, corrected QT interval (QTc) > 440 msec if male or 450 msec if female, prevalence rate (PR) > 220 msec or any rhythm other than sinus rhythm, sinus bradycardia (HR <40 bpm), or sinus arrhythmia.
- Subjects with a history of alcohol consumption exceeding 14 drinks/week on average within the 6 months before study entry.
- Subjects whose sitting blood pressure is above 140/90 mmHg on 2 evaluations at least 10 minutes apart at screening.
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- Subjects who have donated blood in excess of 500 mL within 60 days prior to the first dose of study medication.
- Subjects with a positive result on drug screen, hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency (HIV) tests
- Subjects who have used prescription or non-prescription drugs, vitamins, herbal supplements or dietary supplements within 14 days prior to the first dose of study medication. Subjects who have used acetaminophen at doses of < 2 grams/day will be eligible for study entry.
- Subjects who have been treated with an investigational drug within 30 days.
- Subjects who have previously received or are currently taking valproic acid.
- Subjects who have a history of drug abuse.
- Subjects who are not willing to abstain from consuming products containing caffeine (including chocolate), methyl xanthine, or alcohol from Day -1 through the end of the pharmacokinetics (PK) study (day 4 for part 1 subjects).
- Subjects who have had a febrile illness within 5 days prior to the first dose of study medication.
- Subjects with inadequate venous access.
- Subjects vaccinated within 30 days prior to the first dose of study medication. -
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan
Ann Arbor, Michigan, 48109
About this study
Official title: A Phase 1, Single Ascending Dose, Double Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1) or Trauma Patients(Part 2)
The purpose of the first part of this study is to determine the safety and tolerability of ascending doses of valproic acid (also known as Depacon) administered as intravenous infusion (IV) in doses ranging from 15 mg/kg to 250 mg/kg in healthy subjects.
The second part of the study will also be to determine the safety and tolerability of single ascending doses of valproic acid administered as IV in trauma subjects with hemorrhagic shock.
Read the detailed description
Part 1 of the study will be a single center study intended to assess the safety and tolerability of valproic acid dosages at 15 mg/kg, 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, 150 mg/kg 180 mg/kg, 210 mg/kg and 250 mg/kg. Up to 72 healthy subjects (9 dose groups of 8 subjects) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 3:1 active drug: placebo.
Part 2 of the study will be a multicenter, double blind, placebo-controlled study in trauma patients with hemorrhagic shock who are able to give consent or severe trauma patients with hemorrhagic shock in whom a legally authorized representative can give consent. Up to 12 patients (2 dose groups of 6 patients) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 2:1 active drug : placebo. The dose levels in Part 2 will be the two highest doses that are demonstrated to have acceptable safety profile based on the review of safety data from Part 1.
- Conditions
- Shock,Hemorrhagic
- Being tested
- Valproic Acid, Isotonic saline solution
- Medical subject headings
- Shock, Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Also called Depacon
By infusion over 1 hour
Isotonic saline solutionDrug
By infusion over 1 hour
| Study group | Role | What they receive |
|---|---|---|
| valproic acid (Depacon) | Experimental | Valproic acid by IV infusion over one hour Receives: Drug: Valproic Acid |
| Isotonic saline solution | Placebo comparator | The placebo administered by IV infusion over 1 hour Receives: Drug: Isotonic saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT)
Dose limiting toxicity (DLT) will be defined as drug-related grade 2 (moderate) or higher toxicity (excluding fever, chills, nausea or other possible infusion-related effects). The maximum tolerated dose (MTD) will be declared at the dose below which 2 or more subjects experience DLT.
Measured: Subjects will be monitored for 4 days after the one hour infusion. Dose escalation may occur if less than 2 subjects in any cohort of 8 experience DLT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Shock,HemorrhagicStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Hasan Alam
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Hasan Alam, University of Michigan
- Investigators
- Hasan Alam, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951560
- Sponsor's protocol ID
- VPA-C-002
- Status last verified
- Dec 2016
- First submitted
- 23 Sep 2013
- Last updated
- 19 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Georgoff PE, Nikolian VC, Bonham T, Pai MP, Tafatia C, Halaweish I, To K, Watcharotone K, Parameswaran A, Luo R, Sun D, Alam HB. Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial. Clin Pharmacokinet. 2018 Feb;57(2):209-219. doi: 10.1007/s40262-017-0553-1.
PubMed 28497259
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single Ascending Dose, Double Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1) or Trauma Patients(Part 2)
- ClinicalTrials.gov ID
- NCT01951560
- Acronym / sponsor ID
- VPA-C-002
- Conditions
- Shock,Hemorrhagic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Dr. Hasan AlamUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 26 Sep 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 purpose of the first part of this study is to determine the safety and tolerability of ascending doses of valproic acid (also known as Depacon) administered as intravenous infusion (IV) in doses ranging from 15 mg/kg to 250 mg/kg in healthy subjects.
The second part of the study will also be to determine the safety and tolerability of single ascending doses of valproic acid administered as IV in trauma subjects with hemorrhagic shock.
Detailed description
Part 1 of the study will be a single center study intended to assess the safety and tolerability of valproic acid dosages at 15 mg/kg, 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, 150 mg/kg 180 mg/kg, 210 mg/kg and 250 mg/kg. Up to 72 healthy subjects (9 dose groups of 8 subjects) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 3:1 active drug: placebo.
Part 2 of the study will be a multicenter, double blind, placebo-controlled study in trauma patients with hemorrhagic shock who are able to give consent or severe trauma patients with hemorrhagic shock in whom a legally authorized representative can give consent. Up to 12 patients (2 dose groups of 6 patients) will receive single doses of valproic acid or placebo via a 60-min IV infusion in a ratio of 2:1 active drug : placebo. The dose levels in Part 2 will be the two highest doses that are demonstrated to have acceptable safety profile based on the review of safety data from Part 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| valproic acid (Depacon) | Experimental | Drug: Valproic AcidValproic acid by IV infusion over one hour |
| Isotonic saline solution | Placebo comparator | Drug: Isotonic saline solutionThe placebo administered by IV infusion over 1 hour |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female volunteers between the ages of 18 and 65 years, inclusive, in good health based on medical history, physical examination, ECG, and routine laboratory tests (blood chemistry, hematology, urinalysis, and drug screen).
- Female subjects must be surgically sterilized or postmenopausal. Criteria for menopause are surgical menopause (hysterectomy, oophorectomy) or age > 45 years with absence of menses for greater than 12 months or a serum follicle stimulating hormone (FSH) elevation > 25m IU/mL.(mIU/mL is the unit used to measure human chorionic gonadotropin (hCG) in pregnancy test). Tubal ligation with menses within the past 12 months is not considered to be surgical sterilization.
- Negative urine pregnancy test in female volunteers
- Body mass index (BMI) between 18 kg/m2 and 30 kg/m2
- Subjects must be non-smokers
Key exclusion criteria (16 listed)
- Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies; however, subjects with untreated, asymptomatic, seasonal allergies may be enrolled).
- Subjects with a-amylase >130 U/L or lipase >300 U/L or creatinine > upper limit of normal (ULN)
- Subjects with >2times ULN aspartate aminotransferase (AST) or alanine amino transferase (ALT) or >1.5 times total bilirubin
- Subjects whose screening ECG demonstrates at least one of the following: heart rate > 100 bpm for more than 30 minutes, (the combination of three of the graphical deflections seen on a typical ECG is called the(QRS)) > 120 msec, corrected QT interval (QTc) > 440 msec if male or 450 msec if female, prevalence rate (PR) > 220 msec or any rhythm other than sinus rhythm, sinus bradycardia (HR <40 bpm), or sinus arrhythmia.
- Subjects with a history of alcohol consumption exceeding 14 drinks/week on average within the 6 months before study entry.
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 |
|---|---|---|
| Valproic AcidAlso: DepaconBy infusion over 1 hour | Drug | valproic acid (Depacon) |
| Isotonic saline solutionBy infusion over 1 hour | Drug | Isotonic saline solution |
Primary outcome
Dose limiting toxicity (DLT)
Time frame: Subjects will be monitored for 4 days after the one hour infusion. Dose escalation may occur if less than 2 subjects in any cohort of 8 experience DLT.
Dose limiting toxicity (DLT) will be defined as drug-related grade 2 (moderate) or higher toxicity (excluding fever, chills, nausea or other possible infusion-related effects). The maximum tolerated dose (MTD) will be declared at the dose below which 2 or more subjects experience DLT.
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 19 Dec 2016.
- Derived from this study: PubMed 28497259Georgoff PE, Nikolian VC, Bonham T, Pai MP, Tafatia C, Halaweish I, To K, Watcharotone K, Parameswaran A, Luo R, Sun D, Alam HB. Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial. Clin Pharmacokinet. 2018 Feb;57(2):209-219. doi: 10.1007/s40262-017-0553-1.
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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.
Hasan Alam, MD principal investigator
University of Michigan
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 Valproic Acid and Isotonic saline solution in people with Shock,Hemorrhagic, run by Dr. Hasan Alam 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 9 inclusion and 16 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 19 Dec 2016. 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. Some participants in this study may receive a placebo. 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?
Dose limiting toxicity (DLT) (time frame: Subjects will be monitored for 4 days after the one hour infusion. Dose escalation may occur if less than 2 subjects in any cohort of 8 experience DLT.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01951560, which also lists 1 linked publication.
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 19 Dec 2016.