Major Depressive DisorderPhase 1CX157-112NCT01633437
Oral Tyramine Pressor Response Study of CX157 Tablets in Healthy Male Volunteers
A Phase 1 study testing CX157 in people with Major Depressive Disorder, run by CeNeRx BioPharma Inc. at 1 site in United States.
Trial summary
The objectives of this study were to examine the cardiovascular sensitivity to oral tyramine after establishment of steady state with CX157 Modified Release (MR) Tablets, 125 mg administered twice per day (BID) in healthy volunteers compared to placebo; and to investigate the general safety, tolerability and… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- CX157
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Oct 2010
- 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 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male between 18 to 50 years of age, inclusive.
- In good general health as ascertained by not clinically significant physical examination (PE) including measurement of vital signs, medical history, clinical laboratory studies, and 12-lead electrocardiogram (ECG).
- Body Mass Index (BMI) ≥22 and ≤30 kg/m2.
- Agree to abstain from consuming either alcohol-containing or caffeine-containing beverages and to adhere to the dietary restrictions.
Who cannot join
- Presence of a significant acute or chronic medical disorder.
- The mean of three consecutive semi-recumbent SBP and diastolic blood pressure (DBP) readings taken five minutes apart over a 10-minute period at Screening and Day -1 exceeds 140 mmHg and 90 mmHg, respectively, and/or is not stable (semi-recumbent SBP exceeds a maximum range of 10 mmHg between the lowest and highest value).
- The mean of three consecutive semi-recumbent SBP and DBP readings taken five minutes apart over a 10-minute period at Screening and Day -1 is <90 mmHg and 60 mmHg, respectively.
- Has the requirement for or use of any prescription medications within 35 days of study initiation or anticipates use of any psychoactive medication during the study.
- Has taken an monoamine oxidase inhibitor (MAOI) within 90 days preceding Period 1, Day 1 of the study.
- Has requirement for any medication contraindicated for use with an MAOI.
Show all 27Show fewer
- Use of any over-the-counter (OTC) medication within 14 days of study drug.
- History of substance abuse or dependence, including alcohol abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, within the past 12 months.
- Use of tobacco products or any nicotine-containing products (e.g., gum, patch) currently or within the prior 6 months.
- Subject is unwilling to stop consumption of alcohol or caffeine/xanthine-containing drinks or foods within 72 hours of dosing of Day 1 (including any type of wines, caffeinated or decaffeinated herbal tea, grapefruit products (e.g., fresh, canned, or frozen), Seville oranges and pomelos).
- Subjects with known adverse events associated with ingestion of tyramine-containing food.
- Subjects with contraindications to administration of adrenergic receptor antagonists such as labetalol (e.g., asthma, obstructive airway disease, severe bradycardia, diabetes).
- Abnormal screening medical/physical examination, unless the abnormality is considered unlikely to be affected by study participation, or to confound interpretation of safety data.
- A clinically significant clinical laboratory or ECG abnormality at screening; includes any of the following:
- Aspartate aminotransferase (AST/SGOT) >2.0 x the upper limit of normal (ULN),
- Alanine aminotransferase (ALT/SGPT) >2.0 x the ULN,
- Alkaline phosphatase (ALP) >2.0 x the ULN,
- Total bilirubin >1.5 x the ULN,
- Serum creatinine >1.5 x the ULN, and
- Blood urea nitrogen (BUN) >1.5 x the ULN.
- Anticipates elective surgery requiring general anesthesia for at least 10 days following the end of study.
- Test positive for: Cannabinoids, cocaine, amphetamines, barbiturates, opiates or benzodiazepines, cotinine, alcohol use, hepatitis B or C, or human immunodeficiency virus (HIV).
- Participation in a clinical investigation within the last 60 days.
- Previous participation in a prior study of CX157.
- Any other condition which, in the investigator's opinion, may place the subject at greater than normal risk of developing complications.
- Donated any blood product (one pint or greater) within the previous 8 weeks.
- Planning to donate any blood product within 8 weeks of end of study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Multiple-Dose, Randomized, Double-Blind, Oral Tyramine Pressor Response Study Comparing CX157 Tablets to Placebo in Healthy Male Volunteers
The objectives of this study were to examine the cardiovascular sensitivity to oral tyramine after establishment of steady state with CX157 Modified Release (MR) Tablets, 125 mg administered twice per day (BID) in healthy volunteers compared to placebo; and to investigate the general safety, tolerability and pharmacokinetic profile of CX157 tablets at steady state compared to placebo.
Read the detailed description
Methodology: The trial was a Phase 1, single center, DB, three-period study of cardiovascular safety following oral administration of encapsulated tyramine prior to treatment with double-blind (DB) study drug (CX157 Modified Release Tablets, 125 mg administered twice per day (BID) or matching placebo administered BID) and the administration of tyramine in yogurt along with a standard meal during the DB study treatment administration, after CX157 reached steady state.
Prior to treatment with DB study treatment, baseline cardiovascular sensitivity to oral tyramine administered in a fasting state was established in 15 subjects during Period 1 Days 1-3. Following completion of Period 1, the study's 12 subjects were randomized to CX157 (10 subjects) or placebo (2 subjects) and treated for six consecutive days (Days 4-9) to reach steady state. Subjects continued their DB study treatment in Period 3 (Days 10-12); however, during this period tyramine was administered to subjects in the fed state on Day 10 (tyramine 20 mg), Day 11 (tyramine 40 mg) and Day 12 (tyramine 80 mg).
The tyramine pressor dose (minimum dose of tyramine necessary to achieve endpoint) for Period 1 was established through a series of three tyramine challenges (24 hours apart) with tyramine doses based upon a predetermined paradigm. During Period 1, untreated fasting subjects received an initial tyramine challenge dose of 400 mg and were monitored for SBP endpoint changes (SBP increase of ≥30 mmHg on three consecutive occasions at least five minutes apart over a 10-minute (i.e., TYR303). If pressor endpoint was achieved, the tyramine challenge dose administered on Period 1 Day 2 was reduced to 200 mg. However, if endpoint was not achieved, the tyramine challenge dose was raised on Period 1 Day 2 to 600 mg. This dose escalation/reduction paradigm was repeated on Period 1 Day 3 based upon the results of Period 1 Day 2 in order to establish the tyramine pressor dose during that period.
During Period 2 (Days 4-9) subjects were treated with CX157 or placebo twice daily to reach the steady state. On Day 8 of Period 2, single-blind yogurt without tyramine was administered with lunch to familiarize subjects and the clinic staff with the procedures for Period 3.
The tyramine challenges for Period 3 Days 10 - 12 began after six consecutive days of treatment with CX157 or placebo twice daily. The tyramine doses for Period 3 were 20, 40, and 80 mg (24 hours apart). The endpoint for Period 3 was the same as described above for Period 1, reaching of the pressor endpoint (i.e., TYR303).
The study planned for 12 healthy male volunteer subjects to be randomized at Period 2. Ten (10) subjects were to be randomized to CX157 MR Tablets, 125 mg and 2 to matching placebo. Approximately 15 subjects were to enter Period 1 in order to ensure randomization of 12 subjects to Period 2 of the study.
- Conditions
- Major Depressive Disorder
- Being tested
- CX157, Placebo
- Keywords
- tyramine, MAOI, cheese effect, depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CX157Drug
CX157 Modified Release Tablet 125 mg administered twice per day on study days 4-11 and in the morning of study day 12.
PlaceboOther
Placebo administered twice per day on study days 4-11 and in the morning of day 12.
| Study group | Role | What they receive |
|---|---|---|
| Sugar pill | Placebo comparator | Not described Receives: Other: Placebo |
| CX157 | Experimental | CX157 is a reversible monoamine oxidase inhibitor (RIMA) in Phase II development for the treatment of depression. Receives: Drug: CX157 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic Blood Pressure (SBP)
SBP was measured every 5 minutes for the first two hours and every 15 minutes for the next two hours post tyramine ingestion on study Days 10 (20 mg tyramine), 11 (40 mg tyramine), and 12 (80 mg tyramine).
Measured: 4 hours post dose on study Days 10, 11, 12
Secondary outcomes (2)
Number of subjects with adverse events as a measure of safety and tolerability of CX157.
Adverse events were collected during the study.
Measured: Study Days 4-12 (during the DB study drug administration)
Cmax, Cmin, Tmax
The full pharmacokinetic (PK) profile was obtained after the morning dose on Day 9. In addition, trough blood samples were obtained before the morning and evening doses on study Days 6, 7, and 8; and before the morning dose on Days 10, 11 and 12.
Measured: Study Days 6-12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2012 (estimated)
- Study startSep 2010
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- CeNeRx BioPharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Gerson, D.O., Principal investigator, Comprehensive Phase One
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01633437
- Sponsor's protocol ID
- CX157-112
- Acronym
- CX157-112
- Status last verified
- Jun 2012
- First submitted
- 28 Jun 2012
- Last updated
- 4 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multiple-Dose, Randomized, Double-Blind, Oral Tyramine Pressor Response Study Comparing CX157 Tablets to Placebo in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT01633437
- Acronym / sponsor ID
- CX157-112 / CX157-112
- Conditions
- Major Depressive Disorder
- Keywords
- tyramine, MAOI, cheese effect, depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- CeNeRx BioPharma Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 4 Jul 2012 (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 objectives of this study were to examine the cardiovascular sensitivity to oral tyramine after establishment of steady state with CX157 Modified Release (MR) Tablets, 125 mg administered twice per day (BID) in healthy volunteers compared to placebo; and to investigate the general safety, tolerability and pharmacokinetic profile of CX157 tablets at steady state compared to placebo.
Detailed description
Methodology: The trial was a Phase 1, single center, DB, three-period study of cardiovascular safety following oral administration of encapsulated tyramine prior to treatment with double-blind (DB) study drug (CX157 Modified Release Tablets, 125 mg administered twice per day (BID) or matching placebo administered BID) and the administration of tyramine in yogurt along with a standard meal during the DB study treatment administration, after CX157 reached steady state.
Prior to treatment with DB study treatment, baseline cardiovascular sensitivity to oral tyramine administered in a fasting state was established in 15 subjects during Period 1 Days 1-3. Following completion of Period 1, the study's 12 subjects were randomized to CX157 (10 subjects) or placebo (2 subjects) and treated for six consecutive days (Days 4-9) to reach steady state. Subjects continued their DB study treatment in Period 3 (Days 10-12); however, during this period tyramine was administered to subjects in the fed state on Day 10 (tyramine 20 mg), Day 11 (tyramine 40 mg) and Day 12 (tyramine 80 mg).
The tyramine pressor dose (minimum dose of tyramine necessary to achieve endpoint) for Period 1 was established through a series of three tyramine challenges (24 hours apart) with tyramine doses based upon a predetermined paradigm. During Period 1, untreated fasting subjects received an initial tyramine challenge dose of 400 mg and were monitored for SBP endpoint changes (SBP increase of ≥30 mmHg on three consecutive occasions at least five minutes apart over a 10-minute (i.e., TYR303). If pressor endpoint was achieved, the tyramine challenge dose administered on Period 1 Day 2 was reduced to 200 mg. However, if endpoint was not achieved, the tyramine challenge dose was raised on Period 1 Day 2 to 600 mg. This dose escalation/reduction paradigm was repeated on Period 1 Day 3 based upon the results of Period 1 Day 2 in order to establish the tyramine pressor dose during that period.
During Period 2 (Days 4-9) subjects were treated with CX157 or placebo twice daily to reach the steady state. On Day 8 of Period 2, single-blind yogurt without tyramine was administered with lunch to familiarize subjects and the clinic staff with the procedures for Period 3.
The tyramine challenges for Period 3 Days 10 - 12 began after six consecutive days of treatment with CX157 or placebo twice daily. The tyramine doses for Period 3 were 20, 40, and 80 mg (24 hours apart). The endpoint for Period 3 was the same as described above for Period 1, reaching of the pressor endpoint (i.e., TYR303).
The study planned for 12 healthy male volunteer subjects to be randomized at Period 2. Ten (10) subjects were to be randomized to CX157 MR Tablets, 125 mg and 2 to matching placebo. Approximately 15 subjects were to enter Period 1 in order to ensure randomization of 12 subjects to Period 2 of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar pill | Placebo comparator | Other: Placebo |
| CX157 | Experimental | Drug: CX157CX157 is a reversible monoamine oxidase inhibitor (RIMA) in Phase II development for the treatment of depression. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male between 18 to 50 years of age, inclusive.
- In good general health as ascertained by not clinically significant physical examination (PE) including measurement of vital signs, medical history, clinical laboratory studies, and 12-lead electrocardiogram (ECG).
- Body Mass Index (BMI) ≥22 and ≤30 kg/m2.
- Agree to abstain from consuming either alcohol-containing or caffeine-containing beverages and to adhere to the dietary restrictions.
Key exclusion criteria (27 listed)
- Presence of a significant acute or chronic medical disorder.
- The mean of three consecutive semi-recumbent SBP and diastolic blood pressure (DBP) readings taken five minutes apart over a 10-minute period at Screening and Day -1 exceeds 140 mmHg and 90 mmHg, respectively, and/or is not stable (semi-recumbent SBP exceeds a maximum range of 10 mmHg between the lowest and highest value).
- The mean of three consecutive semi-recumbent SBP and DBP readings taken five minutes apart over a 10-minute period at Screening and Day -1 is <90 mmHg and 60 mmHg, respectively.
- Has the requirement for or use of any prescription medications within 35 days of study initiation or anticipates use of any psychoactive medication during the study.
- Has taken an monoamine oxidase inhibitor (MAOI) within 90 days preceding Period 1, Day 1 of the study.
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 |
|---|---|---|
| CX157CX157 Modified Release Tablet 125 mg administered twice per day on study days 4-11 and in the morning of study day 12. | Drug | CX157 |
| PlaceboPlacebo administered twice per day on study days 4-11 and in the morning of day 12. | Other | Sugar pill |
Primary outcome
Systolic Blood Pressure (SBP)
Time frame: 4 hours post dose on study Days 10, 11, 12
SBP was measured every 5 minutes for the first two hours and every 15 minutes for the next two hours post tyramine ingestion on study Days 10 (20 mg tyramine), 11 (40 mg tyramine), and 12 (80 mg tyramine).
2 secondary outcomes
Number of subjects with adverse events as a measure of safety and tolerability of CX157.
Time frame: Study Days 4-12 (during the DB study drug administration)
Cmax, Cmin, Tmax
Time frame: Study Days 6-12
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 4 Jul 2012.
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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.
William Gerson, D.O. principal investigator
Comprehensive Phase One
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 CX157 in people with Major Depressive Disorder, run by CeNeRx BioPharma 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 4 inclusion and 27 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 4 Jul 2012. 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?
Systolic Blood Pressure (SBP) (time frame: 4 hours post dose on study Days 10, 11, 12). 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 4 Jul 2012.