MigrainesPhase 1NCT04201080
A Trial to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous TRV250
A Phase 1 study testing Part A: TRV250-20mg/ml, Part B: TRV250 Dose 1 and Part B: TRV250 Dose 2 in people with Migraines, run by Trevena Inc. at 1 site in United Kingdom.
Trial summary
A trial to assess the efficacy, safety, tolerability and effect of a drug (code name TRV250) given as an injection to subjects who have received an injection of a drug called glyceryl trinitrate (GTN) which is clinically known to induce an immediate headache of short duration (under 30 minutes), known as the "GTN… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Migraines
- What is being tested?
- Part A: TRV250-20mg/ml, Part B: TRV250 Dose 1 and Part B: TRV250 Dose 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Nov 2019to 10 Aug 2020
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient is male or female, aged between 18 and 55 years inclusive.
- Patient's Body Mass Index (BMI) is between 18 and 32 kg/m2 inclusive.
- Patient should have a clinical diagnosis of migraine without aura (IHS criteria 1.1) and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).
Who cannot join
- Patient has previous exposure to TRV250.
- Abnormal EEG at screening or risk factors of increased seizure potential, such as previous seizures, history of febrile seizures, cerebral tumor, stroke, cerebrovascular disease, or significant traumatic brain injury.
- Patient with a history of hypotension or hypertension, including where this is currently under control.
- Patient taking prophylactic migraine treatments such as beta blockers 28 days before GTN infusion on Day 1.
- Resting heart rate <45 beats per minute on assessment of vital signs at screening or pre-GTN infusion on Day 1.
- QTcF >450 msec at screening (mean of three ECGs) or pre-GTN infusion on Day 1.
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- Patient with another headache disorder such as menstrual migraine, chronic migraine, cluster headache, tension headache or other chronic headache states.
- Patient who have a history, or family history of any vascular intracranial lesion such as subarachnoid aneurysm or similar and patients with a relevant neurological history.
- Patients who have any allergies/contraindications for Triptan administration.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
MAC Clinical Research Manchester (Early Phase Unit), Neuroscience Centre of Excellence
Manchester, Greater Mancherster, M13 9NQ
About this study
Official title: A Phase 1, Two-part, Single Dose, Randomised, Double-blind, Placebo-controlled Parallel Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Subcutaneous TRV250 Following Glyceryl Trinitrate Infusion
A trial to assess the efficacy, safety, tolerability and effect of a drug (code name TRV250) given as an injection to subjects who have received an injection of a drug called glyceryl trinitrate (GTN) which is clinically known to induce an immediate headache of short duration (under 30 minutes), known as the "GTN immediate headache"
Read the detailed description
This is a Phase 1, two-part, single dose, randomised, double-blind, placebo-controlled parallel study to evaluate the efficacy, safety, tolerability and pharmacokinetics of subcutaneous TRV250 following glyceryl trinitrate infusion-evoked migraine type headache.
Approximately 360 patients (120 in Part A and 240 in Part B) are planned to complete dosing and assessments.
Part A will be a proof of concept study; approximately 120 patients will be randomised to 1 of 2 treatments (60 patients per treatment arm). Patients will receive either TRV250 (20 mg) or placebo administered subcutaneously in a double-blind manner. Part B will be a dose-ranging study; approximately 240 patients will be randomised to 1 of 4 treatments (60 patients per treatment arm). Patients will receive 1 of 3 doses of TRV250 or placebo administered subcutaneously in a double-blind manner.
The study will consist of 3 phases: Screening, Confinement, and Follow-Up. Patients will participate in an outpatient Screening visit, a 3-day inpatient Confinement Phase that comprises GTN-infusion and treatment with TRV250 or placebo, and an outpatient safety Follow-Up visit 5 to 7 days post-dose.
The expected duration of participation is up to 6 weeks.
The diagnosis and criteria for inclusion covers male and female patients aged 18-55 years (inclusive), with a body mass index (BMI) within the range 18-32 kg/m2 inclusive at Screening. The patient must experience a migraine without aura as defined by International Headache Society (IHS) criteria 1.1 and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).
The investigational product (TRV250) will be administered by subcutaneous injection (10 mg/ml per injection). In Part A, 2 injections will be administered to deliver a single dose of 20 mg. In Part B, the dose levels to be administered will be decided following interim analysis of the data collected in Part A; however, the doses selected will not exceed that administered in Part A (up to 2 injections will be administered to deliver a single dose of up to 20 mg). Matched placebo injections will be administered by subcutaneous injections to maintain blinding.
By virtue of this being an exploratory study for the purpose of estimation and prediction, Bayesian estimates along with posterior predictive probabilities will be provided to address the primary and secondary efficacy objectives, as appropriate. Standard descriptive statistics will be provided to assess secondary safety and pharmacokinetic objectives.
Interim analyses will be conducted at the end of Part A of the study prior to proceeding to Part B. Preliminary pharmacokinetics (using nominal times) will be conducted to estimate the AUCt, AUC∞, Cmax, and t1/2. These preliminary efficacy, pharmacokinetic, safety and tolerability data will be evaluated unblinded at the end of Part A and shared with the Investigators in an unblinded manner, prior to starting Part B.
Once the study is complete, pharmacokinetic analyses will be completed using actual collection times.
In Part A, the difference in treatment proportions of patients who experience a headache occurring up to 4 hours post-dose will be tested using a chi-square. If the patient requires rescue medication then the patient will be considered a non-responder. In Part B, a Bayesian approach will be utilized using the prior information obtain from Part A. The proportion of patients who experience a headache occurring up to 4 hours post-dose, will be modelled using a Bayesian hierarchical logistic regression. This logistic regression will include a continuous covariate for TRV250 dose where Placebo is considered to be 0 mg of TRV250. If the patient requires rescue medication then the patient will be considered a non-responder.
Demographic and baseline data will be listed and summarised descriptively. Safety and tolerability assessments will be listed and summarised descriptively by treatment group as the observations and when appropriate, as the change from baseline. Plasma PK parameter values will be listed and summarised by treatment group. Dose proportionality may be assessed with a power model and slope analysis.
Safety laboratory tests will be tabulated and any out of range values highlighted. Clinically significant changes in safety laboratory results will be recorded as AEs.
- Conditions
- Migraines
- Being tested
- Part A: TRV250-20mg/ml, Placebo, Part B: TRV250 Dose 1, Part B: TRV250 Dose 2, Part B: TRV250 Dose 3
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A: TRV250-20mg/mlDrug
Also called Proof of concept
TRV250 SC Injections
PlaceboDrug
Also called Proof of concept
Placebo SC injections
Part B: TRV250 Dose 1Drug
Also called Dose-ranging
Dose 1of3 TRV250
Part B: TRV250 Dose 2Drug
Also called Dose-ranging
Dose 2of3 TRV250 SC injections
Part B: TRV250 Dose 3Drug
Also called Dose-ranging
Dose 3of3 TRV250 SC injections
PlaceboDrug
Also called Dose-ranging
Placebo SC injections
| Study group | Role | What they receive |
|---|---|---|
| Part A: TRV250 for SC injection | Experimental | 2 SC injections of (10 mg/ml per injection) Receives: Drug: Part A: TRV250-20mg/ml |
| Part A: Placebo for SC injection | Placebo comparator | 2 SC injections (identical to the TRV250) Receives: Drug: Placebo |
| Part B: TRV250 dose 1 for SC injection | Experimental | 1 of 3 doses of TRV250 (using 2 identical syringes) Receives: Drug: Part B: TRV250 Dose 1 |
| Part B: TRV250 dose 2 for SC injection | Experimental | 1 of 3 doses of TRV250 (using 2 identical syringes) Receives: Drug: Part B: TRV250 Dose 2 |
| Part B: TRV250 dose 3 for SC injection | Experimental | 1 of 3 doses of TRV250 (using 2 identical syringes) Receives: Drug: Part B: TRV250 Dose 3 |
| Part B: Placebo for SC injection | Placebo comparator | Placebo (using syringes identical to the TRV250 arms) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points.
Verbal Numerical Rating (NRS) and Headache Characteristics (Pain Response, Pain Freedom, Nausea, Photophobia) Assessment: 0 minutes prestart of GTN infusion and every 15 minutes until 4 hours post-dose
Measured: 0-4 hours post-dose
Secondary outcomes (18)
The proportion of patients who experienced a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥2 points
NRS Headache Rating and Characteristics: 0 Minutes (mins) pre-start of GTN, every 15mins to 4 hours (hrs) post-dose, every 30mins to 8hrs post-dose
Measured: 0-8 hours post-dose
The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥3 points.
NRS Headache Rating and Characteristics: 0 Minutes (mins) pre-start of GTN, every 15mins to 4 hours (hrs) post-dose, every 30mins to 8hrs post-dose
Measured: 0-8 hours post-dose
The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥4 points.
NRS Headache Rating and Characteristics: 0 Minutes (mins) pre-start of GTN, every 15mins to 4 hours (hrs) post-dose, every 30mins to 8hrs post-dose
Measured: 0-8 hours post-dose
Pain Response (PR) at 2-hour time point following injection of TRV250 or placebo
Two-hour pain response (2HPR; pain response is defined as reduction in migraine type headache severity from verbal NRS score of ≥4 points at 60 minutes post-start of GTN infusion to ≤3 at 24 hours of follow-up)
Measured: every 2 hours for 24 hours
PF at 2-hour time point following injection of TRV250 or placebo.
Two-hour pain freedom (2HPF; pain freedom is defined as reduction in migraine type headache severity from verbal NRS score of ≥4 points at 60 minutes post-start of GTN infusion to ≤1 at 24 hours of follow-up)
Measured: every 2 hours for 24 hours
Sustained pain response between 2 and 24 hours (2-24H SPR): PR at 2 hours after TRV250 or placebo administration, with no administration of any rescue medication and no occurrence of migraine type headache with verbal NRS score of ≥4 points
Sustained pain response between 2 and 24 hours
Measured: up to 24 hours post dose
Absence of nausea between 2 and 24 hours in patients with nausea from 60 minutes post-start of GTN infusion
Absence of nausea between 2 and 24 hours
Measured: up to 24 hours post dose
Absence of photophobia between 2 and 24 hours in patients with photophobia from 60 minutes post-start of GTN infusion.
Absence of photophobia between 2 and 24 hours
Measured: up to 24 hours post dose
Proportion of patients requiring use of rescue medication at various timepoints.
Proportion of patients requiring use of rescue medication at various timepoints.
Measured: up to 24 hours of follow-up
The effect of TRV250 on cardiac repolarisation determined from cardiac telemetry
Patients will be monitored by cardiac telemetry beginning on Day -1 for a minimum of 8 hours pre-GTN infusion and for a minimum of 24 hours post- study drug administration. Any events on cardiac telemetry will be printed and recorded. All cardiac telemetry data will be stored and may be analysed later in the development of TRV250 to evaluate potential drug effects on cardiac conduction and/or as needed to evaluate correlations between cardiac rhythm and symptoms (such as dizziness or palpitations).
Measured: Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose
The effect of TRV250 on cardiac repolarisation (Cardiac Telemetry)
The effect of TRV250 on cardiac repolarisation as determined from cardiac telemetry. Cardiac telemetry will begin on Day -1 a minimum of 8 hours pre-GTN infusion and for 24 hours post-dose. Any events on cardiac telemetry will be printed and recorded. All cardiac telemetry data will be stored and may be analysed later in the development of TRV250 to evaluate potential drug effects on cardiac conduction and/or as needed to evaluate correlations between cardiac rhythm and symptoms (such as dizziness or palpitations).
Measured: Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose
The effect of TRV250 on cardiac repolarisation (Electrocardiogram)
The effect of TRV250 on cardiac repolarisation as determined from Electrocardiogram (ECG) to check TRV250 effect on the prolongation of QT interval. A 12-lead ECG will be collected at Screening and Day 1 pre-GTN infusion in triplicate, approximately 1 minute apart. ECG will also be collected at single timepoints of: 1-hour, 4-hour and 24-hours post-dose. 12-lead ECGs should be obtained after the patient has rested in the supine position for at least 5 minutes.
Measured: 12-lead ECG: screening, Day-1 and up to 24 hours post dose
Safety Assessment - Injection Site Assessment
of pain, tenderness, erythema/redness, and induration/swelling at the injection sites will be conducted pre-GTN infusion, and at 0 hours up to at least 24 hours post-dose.
Measured: at time of GTN-infusion (0 hours) up to 24hrs post-dose
The PK data model for each patient/dose combination: AUC(0-∞)
AUC from 0 to time infinity (ng∙hr/mL) at Pre-dose, 0.25, btwn 1-3hrs, btwn 6-12hrs, 24hrs
Measured: up to 24 hours post dose
The PK data model for each patient/dose combination: AUC(0-24)
AUC from 0 to 24 hrs post-dose (ng∙hr/mL) at Pre-dose, 0.25, btwn 1-3hrs, btwn 6-12hrs, 24hrs
Measured: up to 24 hours post dose
The PK data model for each patient/dose combination: Cmax (ng/mL) o Tmax - Time of maximum concentration (hours) o t1/2 - half-life (hours)
Cmax (ng/mL) at Pre-dose, 0.25, btwn 1-3hrs, btwn 6-12hrs, 24hrs
Measured: up to 24 hours post dose
The PK data model for each patient/dose combination: Tmax
Time of maximum concentration (hours) at Pre-dose, 0.25, btwn 1-3hrs, btwn 6-12hrs, 24hrs
Measured: up to 24 hours post dose
The PK data model for each patient/dose combination: t1/2
half-life (hours) at Pre-dose, 0.25, btwn 1-3hrs, btwn 6-12hrs, 24hrs
Measured: up to 24 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2019
- Study start11 Nov 2019
- Primary completion17 Feb 2020
- Study completion10 Aug 2020
Why it stopped: Because there have been significant enrollment struggles which has been exacerbated by the COVID impact. This has caused an undue delay to the study timelines and its enrollment goals beyond the business needs.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigrainesStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study consists of 2 parts: Part A is a proof of concept study; and Part B will be a dose ranging study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trevena Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dasyam, MBBS, Msc, Principal investigator, MAC Clinical Research Manchester (Early Phase Unit)Nicklas, RN BSN CCRC, Study director, Trevena Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04201080
- Sponsor's protocol ID
- CP250-1002
- Status last verified
- Sep 2021
- First submitted
- 5 Dec 2019
- Last updated
- 22 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Two-part, Single Dose, Randomised, Double-blind, Placebo-controlled Parallel Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Subcutaneous TRV250 Following Glyceryl Trinitrate Infusion
- ClinicalTrials.gov ID
- NCT04201080
- Acronym / sponsor ID
- CP250-1002
- Conditions
- Migraines
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Because there have been significant enrollment struggles which has been exacerbated by the COVID impact. This has caused an undue delay to the study timelines and its enrollment goals beyond the business needs.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Trevena Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Nov 2019 (actual)
- Primary completion
- 17 Feb 2020 (actual)
- Study completion
- 10 Aug 2020 (actual)
- First posted
- 17 Dec 2019 (actual)
- 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.
A trial to assess the efficacy, safety, tolerability and effect of a drug (code name TRV250) given as an injection to subjects who have received an injection of a drug called glyceryl trinitrate (GTN) which is clinically known to induce an immediate headache of short duration (under 30 minutes), known as the "GTN immediate headache"
Detailed description
This is a Phase 1, two-part, single dose, randomised, double-blind, placebo-controlled parallel study to evaluate the efficacy, safety, tolerability and pharmacokinetics of subcutaneous TRV250 following glyceryl trinitrate infusion-evoked migraine type headache.
Approximately 360 patients (120 in Part A and 240 in Part B) are planned to complete dosing and assessments.
Part A will be a proof of concept study; approximately 120 patients will be randomised to 1 of 2 treatments (60 patients per treatment arm). Patients will receive either TRV250 (20 mg) or placebo administered subcutaneously in a double-blind manner. Part B will be a dose-ranging study; approximately 240 patients will be randomised to 1 of 4 treatments (60 patients per treatment arm). Patients will receive 1 of 3 doses of TRV250 or placebo administered subcutaneously in a double-blind manner.
The study will consist of 3 phases: Screening, Confinement, and Follow-Up. Patients will participate in an outpatient Screening visit, a 3-day inpatient Confinement Phase that comprises GTN-infusion and treatment with TRV250 or placebo, and an outpatient safety Follow-Up visit 5 to 7 days post-dose.
The expected duration of participation is up to 6 weeks.
The diagnosis and criteria for inclusion covers male and female patients aged 18-55 years (inclusive), with a body mass index (BMI) within the range 18-32 kg/m2 inclusive at Screening. The patient must experience a migraine without aura as defined by International Headache Society (IHS) criteria 1.1 and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).
The investigational product (TRV250) will be administered by subcutaneous injection (10 mg/ml per injection). In Part A, 2 injections will be administered to deliver a single dose of 20 mg. In Part B, the dose levels to be administered will be decided following interim analysis of the data collected in Part A; however, the doses selected will not exceed that administered in Part A (up to 2 injections will be administered to deliver a single dose of up to 20 mg). Matched placebo injections will be administered by subcutaneous injections to maintain blinding.
By virtue of this being an exploratory study for the purpose of estimation and prediction, Bayesian estimates along with posterior predictive probabilities will be provided to address the primary and secondary efficacy objectives, as appropriate. Standard descriptive statistics will be provided to assess secondary safety and pharmacokinetic objectives.
Interim analyses will be conducted at the end of Part A of the study prior to proceeding to Part B. Preliminary pharmacokinetics (using nominal times) will be conducted to estimate the AUCt, AUC∞, Cmax, and t1/2. These preliminary efficacy, pharmacokinetic, safety and tolerability data will be evaluated unblinded at the end of Part A and shared with the Investigators in an unblinded manner, prior to starting Part B.
Once the study is complete, pharmacokinetic analyses will be completed using actual collection times.
In Part A, the difference in treatment proportions of patients who experience a headache occurring up to 4 hours post-dose will be tested using a chi-square. If the patient requires rescue medication then the patient will be considered a non-responder. In Part B, a Bayesian approach will be utilized using the prior information obtain from Part A. The proportion of patients who experience a headache occurring up to 4 hours post-dose, will be modelled using a Bayesian hierarchical logistic regression. This logistic regression will include a continuous covariate for TRV250 dose where Placebo is considered to be 0 mg of TRV250. If the patient requires rescue medication then the patient will be considered a non-responder.
Demographic and baseline data will be listed and summarised descriptively. Safety and tolerability assessments will be listed and summarised descriptively by treatment group as the observations and when appropriate, as the change from baseline. Plasma PK parameter values will be listed and summarised by treatment group. Dose proportionality may be assessed with a power model and slope analysis.
Safety laboratory tests will be tabulated and any out of range values highlighted. Clinically significant changes in safety laboratory results will be recorded as AEs.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
- Model description
- The study consists of 2 parts: Part A is a proof of concept study; and Part B will be a dose ranging study
| Arm | Type | Receives |
|---|---|---|
| Part A: TRV250 for SC injection | Experimental | Drug: Part A: TRV250-20mg/ml2 SC injections of (10 mg/ml per injection) |
| Part A: Placebo for SC injection | Placebo comparator | Drug: Placebo2 SC injections (identical to the TRV250) |
| Part B: TRV250 dose 1 for SC injection | Experimental | Drug: Part B: TRV250 Dose 11 of 3 doses of TRV250 (using 2 identical syringes) |
| Part B: TRV250 dose 2 for SC injection | Experimental | Drug: Part B: TRV250 Dose 21 of 3 doses of TRV250 (using 2 identical syringes) |
| Part B: TRV250 dose 3 for SC injection | Experimental | Drug: Part B: TRV250 Dose 31 of 3 doses of TRV250 (using 2 identical syringes) |
| Part B: Placebo for SC injection | Placebo comparator | Drug: PlaceboPlacebo (using syringes identical to the TRV250 arms) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patient is male or female, aged between 18 and 55 years inclusive.
- Patient's Body Mass Index (BMI) is between 18 and 32 kg/m2 inclusive.
- Patient should have a clinical diagnosis of migraine without aura (IHS criteria 1.1) and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).
Key exclusion criteria (9 listed)
- Patient has previous exposure to TRV250.
- Abnormal EEG at screening or risk factors of increased seizure potential, such as previous seizures, history of febrile seizures, cerebral tumor, stroke, cerebrovascular disease, or significant traumatic brain injury.
- Patient with a history of hypotension or hypertension, including where this is currently under control.
- Patient taking prophylactic migraine treatments such as beta blockers 28 days before GTN infusion on Day 1.
- Resting heart rate <45 beats per minute on assessment of vital signs at screening or pre-GTN infusion on Day 1.
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 |
|---|---|---|
| Part A: TRV250-20mg/mlAlso: Proof of conceptTRV250 SC Injections | Drug | Part A: TRV250 for SC injection |
| PlaceboAlso: Proof of conceptPlacebo SC injections | Drug | Part A: Placebo for SC injection |
| Part B: TRV250 Dose 1Also: Dose-rangingDose 1of3 TRV250 | Drug | Part B: TRV250 dose 1 for SC injection |
| Part B: TRV250 Dose 2Also: Dose-rangingDose 2of3 TRV250 SC injections | Drug | Part B: TRV250 dose 2 for SC injection |
| Part B: TRV250 Dose 3Also: Dose-rangingDose 3of3 TRV250 SC injections | Drug | Part B: TRV250 dose 3 for SC injection |
| PlaceboAlso: Dose-rangingPlacebo SC injections | Drug | Part B: Placebo for SC injection |
Primary outcome
The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points.
Time frame: 0-4 hours post-dose
Verbal Numerical Rating (NRS) and Headache Characteristics (Pain Response, Pain Freedom, Nausea, Photophobia) Assessment: 0 minutes prestart of GTN infusion and every 15 minutes until 4 hours post-dose
18 secondary outcomes
The proportion of patients who experienced a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥2 points
Time frame: 0-8 hours post-dose
The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥3 points.
Time frame: 0-8 hours post-dose
The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥4 points.
Time frame: 0-8 hours post-dose
Pain Response (PR) at 2-hour time point following injection of TRV250 or placebo
Time frame: every 2 hours for 24 hours
PF at 2-hour time point following injection of TRV250 or placebo.
Time frame: every 2 hours for 24 hours
Sustained pain response between 2 and 24 hours (2-24H SPR): PR at 2 hours after TRV250 or placebo administration, with no administration of any rescue medication and no occurrence of migraine type headache with verbal NRS score of ≥4 points
Time frame: up to 24 hours post dose
Absence of nausea between 2 and 24 hours in patients with nausea from 60 minutes post-start of GTN infusion
Time frame: up to 24 hours post dose
Absence of photophobia between 2 and 24 hours in patients with photophobia from 60 minutes post-start of GTN infusion.
Time frame: up to 24 hours post dose
Proportion of patients requiring use of rescue medication at various timepoints.
Time frame: up to 24 hours of follow-up
The effect of TRV250 on cardiac repolarisation determined from cardiac telemetry
Time frame: Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose
The effect of TRV250 on cardiac repolarisation (Cardiac Telemetry)
Time frame: Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose
The effect of TRV250 on cardiac repolarisation (Electrocardiogram)
Time frame: 12-lead ECG: screening, Day-1 and up to 24 hours post dose
Safety Assessment - Injection Site Assessment
Time frame: at time of GTN-infusion (0 hours) up to 24hrs post-dose
The PK data model for each patient/dose combination: AUC(0-∞)
Time frame: up to 24 hours post dose
The PK data model for each patient/dose combination: AUC(0-24)
Time frame: up to 24 hours post dose
The PK data model for each patient/dose combination: Cmax (ng/mL) o Tmax - Time of maximum concentration (hours) o t1/2 - half-life (hours)
Time frame: up to 24 hours post dose
The PK data model for each patient/dose combination: Tmax
Time frame: up to 24 hours post dose
The PK data model for each patient/dose combination: t1/2
Time frame: up to 24 hours post dose
Results and safety
The study was stopped early (reason given: Because there have been significant enrollment struggles which has been exacerbated by the COVID impact. This has caused an undue delay to the study timelines and its enrollment goals beyond the business needs.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- Individual participant dataSharing planned: No
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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.
Dasyam, MBBS, Msc principal investigator
MAC Clinical Research Manchester (Early Phase Unit)
Nicklas, RN BSN CCRC study director
Trevena Inc.
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 Part A: TRV250-20mg/ml, Part B: TRV250 Dose 1 and Part B: TRV250 Dose 2 in people with Migraines, run by Trevena Inc. at 1 site in United Kingdom.
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 3 inclusion and 9 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: stopped early, as of the sponsor's last update on 22 Sep 2021. 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 Kingdom. 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 was stopped early (reason given: Because there have been significant enrollment struggles which has been exacerbated by the COVID impact. This has caused an undue delay to the study timelines and its enrollment goals beyond the business needs.). Results are not available in the source record.
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?
The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points. (time frame: 0-4 hours post-dose). 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 22 Sep 2021.