Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Sativex Low Dose, Nabiximols, GW-1000-02, GW-10000-02
Sativex · 33 trials · 18 indications
LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-6 score is being reported. Negative values indicate an improvement in muscle tone.
The spasticity 0-10 NRS was completed daily at bedtime using a paper study diary. The difference between spasticity and spasm was clearly explained to the caregiver. The primary caregiver was asked the following question: "This question is about your child's muscles and how soft or tight/hard they have felt today. Think carefully about how your child's muscles have felt today and circle a number from 0 to 10 that best describes this, where: 0 = 'my child's muscles have felt totally relaxed' and 10 = 'my child's muscles have felt the tightest/hardest they have ever felt'". A reduction in score indicates an improvement in condition. The mean spasticity 0-10 NRS score of the last 7 days of the baseline period was used for a patient's mean baseline score. The mean 0-10 NRS score of the last 7 days prior to completion/withdrawal was used for a patient's mean end of treatment score.
Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.
Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/Baseline pain NRS mean \* 100. For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew, unrelated to disease progression, before end of Week 5 (no diary data from Day 33 onwards), Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.
Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.
Subjects were asked "On a scale of '0 to 10' please indicate the average level of your spasticity over the last 24 hours" with the anchors: 0 = 'no spasticity' and 10 = 'worst possible spasticity'. They were asked to relate 'no spasticity' to the time prior to the onset of their spasticity.
The time to treatment failure was calculated as the number of days from the first day of treatment up to the day of treatment failure. The day of treatment failure was the earliest of:the day of premature cessation of study medication;the first day of the longest period, ending on the last day of treatment, where the mean spasticity NRS had increased by at least 20% and at least 1 unit from the treatment baseline; the day of a clinically relevant increase in anti-spasticity or disease modifying medication. The number of subjects who failed treatment were calculated.
The pain severity Numerical Rating Scale was complete at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain severity in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of neuropathic pain. A negative value indicates an improvement in pain score from baseline.
The pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. A negative value indicates an improvement in pain score from baseline.
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. The pain NRS was completed at the same time each day, i.e. bedtime in the evening.
The average pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.
The peripheral neuropathic pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.
The diabetic neuropathy pain Numerical Rating Scale was complete at the end of every day. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your nerve pain due to diabetes in the last 24 hours" where 0 = no pain and 10 = worst possible pain. No pain relates to the time prior to the onset of pain due to diabetic neuropathy. For those whose evaluable period ended before Day 7, the mean of the available post-randomisation data was used. Those with no post-baseline diary pain 0-10 Numerical Rating Scale scores were excluded from the analysis.
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening. Estimates were produced for a one-week period, with the evaluable period finishing at the end of the appropriate seven-day period.
The average spasticity NRS was completed at the same time each day, i.e. bedtime in the evening. The subject was asked "on a scale of '0 to 10', please indicate the number that best describes your spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst possible spasticity. A negative value indicates an improvement in pain score from baseline.
To assess the effect of Sativex in neurogenic overactive bladder, the incontinence episode frequency was selected as the primary endpoint. Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = 'No Pain' and 10 = 'Worst Possible Pain'. Patients were instructed to relate 'No Pain' to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.
The spasticity Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.
The neuropathic pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = worst possible pain. A negative value indicates an improvement in pain score from baseline.
The number of subjects who experienced an adverse event in this study is presented.
The average pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. A negative value indicates an improvement in pain score from baseline.
Each day, in the morning (on waking), at lunchtime and in the evening (just before going to bed), patients recorded in their patient diary their level of pain using a Box Scale-11 pain score ranging from zero "no pain" to 10 "worst possible pain". Week 3 analysis was defined as the mean of the last seven days in the study. The last day was taken as the last day with complete diary card pain data that occurred on or before the last day the patient took study medication. A negative value from baseline indicates and improvement.
The pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. A negative value indicates an improvement in pain score from baseline.
Subjects recorded their use of escape medication each day on their diary card.
Following data entry, all adverse events were medically encoded using the Medical Dictionary for Regulatory Activities (MedDRA) 6.0. All subjects who experienced an adverse event during the treatment period is presented.
Each day patients recorded in their patient diary, the severity of their pain during the previous 24 hours using a Box Scale-11 pain score ranging from zero "no pain at all" to 10 "pain as bad as you can imagine". The Box Scale-11 pain score endpoint for each assessment period was the average of all available data recorded during the seven whole days prior to the visit immediately subsequent to that period, but only including data from Day 8 onwards. A negative value indicates an improvement in pain score from baseline.
The number of patients who experienced an adverse event during the course of this extension study is presented
This was achieved by measuring the change from baseline after six weeks of therapy in the severity of the primary impairment, a composite score from one of five Multiple Sclerosis symptom categories that subjects nominated as their most severe symptom. The severity scores were recorded using a 100 mm Visual Analogue Scale, where 0 = no problem and 100 = very bad. A decrease in score indicates an improvement.
This was achieved by measuring the change in the Part A study score (mean of all scores during the last two weeks of six weeks of double-blind therapy) in the severity of the primary impairment (mean of all scores during the last two weeks of four weeks of open-label therapy), a composite score from one of five multiple sclerosis symptom categories that subjects nominated as their most severe symptom. The severity scores were recorded using a 100 mm Visual Analogue Scale, where 0 = no problem and 100 = very bad. As such, a decrease in score indicates an improvement and a negative value indicates an improvement in score from baseline.
To establish whether the addition of cannabinoids (Nabiximols) to standard TMZ treatment improves overall survival time (OS) in MGMT methylated recurrent GBM compared to the addition of placebo to TMZ.
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 5 (last 3 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening.
Adverse events will be coded according to the current medical dictionary for regular activities graded using the Common Terminology Criteria for Adverse Events criteria. The number of patients who experienced an adverse event whilst on treatment will be presented.
Adverse events will be coded according to the current medical dictionary for regular activities graded using the Common Terminology Criteria for Adverse Events criteria. The number of patients who experienced an adverse event whilst on treatment will be presented.
All blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For pharmacokinetic (PK) assessments, blood will be drawn from each patient into a five mL lithium-heparinised tube at the following intervals (±five min): Pre-dose (0),0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 11, 24, 36 and 48 hours post dose. Collected blood samples will be used to confirm correct dosing, and to provide information about the plasma concentrations of unbound THC, CBD, 11-hydroxy-THC (11-OH-THC), 6-hydroxy-CBD (6-OH-CBD) and 7-hydroxy-CBD (7-OH-CBD).
All blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For pharmacokinetic (PK) assessments, blood will be drawn from each patient into a five mL lithium-heparinised tube at the following intervals (±five min): Pre-dose (0),0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 11, 24, 36 and 48 hours post dose. Collected blood samples will be used to confirm correct dosing, and to provide information about the plasma concentrations of unbound THC, CBD, 11-OH-THC, 6-OH-CBD and 7-OH-CBD.
All blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. For pharmacokinetic (PK) assessments, blood will be drawn from each patient into a five mL lithium-heparinised tube at the following intervals (±five min): Pre-dose (0),0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 11, 24, 36 and 48 hours post dose. Collected blood samples will be used to confirm correct dosing, and to provide information about the plasma concentrations of unbound THC, CBD, 11-OH-THC, 6-OH-CBD and 7-OH-CBD.
Mean difference in Mean peak effect (Emax) between: Marinol 20 mg vs Sativex 21.6 mg; Marinol 20 mg vs Sativex 43.2 mg; Marinol 40 mg vs Sativex 43.2 mg.
Mean difference in Mean peak effect (Emax) between: Marinol 20 mg vs Sativex 21.6 mg; Marinol 20 mg vs Sativex 43.2 mg; Marinol 40 mg vs Sativex 43.2 mg.
Mean difference in Mean peak effect (Emax) between: Marinol 20 mg vs Sativex 21.6 mg; Marinol 20 mg vs Sativex 43.2 mg; Marinol 40 mg vs Sativex 43.2 mg.
| Arm | Type | Description |
|---|---|---|
| Nabiximols | EXPERIMENTAL | Nabiximols is a complex botanical medicine formulated from extracts of the cannabis plant that contains the principal cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and also contains minor constituents, including other cannabinoid and non-cannabinoid plant components, such as terpenes, sterols, and triglycerides. Each spray delivers 100 microliters (μL) of nabiximols. Nabiximols will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. |
| Placebo | PLACEBO_COMPARATOR | Placebo to match nabiximols will be presented as an oromucosal spray containing the excipients ethanol and propylene glycol (50% v/v) with colorings and flavored with peppermint oil (0.05% v/v). Each spray will deliver 100 μL containing no active ingredients. Placebo will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks. |
| Sativex | ACTIVE_COMPARATOR | Oromucosal spray containing delta-9-tetrahydrocannabinol (THC) (27 mg/mL):cannabidiol (CBD) (25 mg/mL). Each 100 μL spray to the sub-lingual or oral mucosa delivered THC 2.7 mg and CBD 2.5 mg. The maximum number of daily sprays was 12. |
| Placebo (GA-0034) | PLACEBO_COMPARATOR | Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings. |
| Non-comparative, open-label Nabiximols | EXPERIMENTAL | Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray, in the morning and evening, up to a maximum of 10 sprays per day for 6 months. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligrams \[mg\]/milliliter \[mL\]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD. |
| A | EXPERIMENTAL | - |
| B | PLACEBO_COMPARATOR | - |
| GW-1000-02 | EXPERIMENTAL | Active treatment. |
| GW-2000-02 | EXPERIMENTAL | Active treatment |
| THC Alone | EXPERIMENTAL | Active treatment |
| Standard Temozolomide with Nabiximols | EXPERIMENTAL | * Temozolomide 150mg/m2 for cycle 1, increasing to 200mg/m2 for subsequent cycles, once daily for days 1-5, orally, at the start of each 28 day cycle, up to a maximum of 6 cycles. * Nabiximols up to 12 oromucosal sprays per day up to a maximum of 6 cycles; self titrated over days 1-14 in cycle 1. |
| Standard Temozolomide with Nabiximols-matched placebo | PLACEBO_COMPARATOR | * Temozolomide 150mg/m2 for cycle 1, increasing to 200mg/m2 for subsequent cycles, once daily for days 1-5, orally, at the start of each 28 day cycle, up to a maximum of 6 cycles. * Nabiximols-matched placebo up to 12 oromucosal sprays per day up to a maximum of 6 cycles; self titrated over days 1-14 in cycle 1. |
| Sativex Low Dose | EXPERIMENTAL | Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD. |
| Sativex Medium Dose | EXPERIMENTAL | Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD. |
| Sativex High Dose | EXPERIMENTAL | Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD. |
| Sativex and Dose-Intense Temozolomide | EXPERIMENTAL | Patients will received Sativex and Dose-Intense Temozolomide in a double-blind manner |
| Placebo and Dose-Intense Temozolomide | PLACEBO_COMPARATOR | Patients will received placebo and Dose-Intense Temozolomide and in double-blind manner |
| Group 1: mild hepatic impairment | ACTIVE_COMPARATOR | Mild hepatic impairment: eight patients of Child-Pugh Grade A (Score 5-6). All patients received Sativex treatment. |
| Group 2: Moderate hepatic impairment | ACTIVE_COMPARATOR | Moderate hepatic impairment: eight patients of Child-Pugh Grade B (Score 7-9). All patients received Sativex treatment. |
| Group 3: Pugh Grade B (Score 7-9). | EXPERIMENTAL | Severe hepatic impairment: eight patients of Child-Pugh Grade C (Score 10-15). All patients received Sativex treatment. |
| Group 4: Control group | ACTIVE_COMPARATOR | Control Group: eight healthy subjects matched with respect to age (±10 years), weight (±10% body mass index \[BMI\]) and sex to the severe or most severe evaluable patients. All patients received Sativex treatment. |
| Sativex 4 sprays | EXPERIMENTAL | - |
| Sativex 8 sprays | EXPERIMENTAL | - |
| Sativex 16 sprays | EXPERIMENTAL | - |
| Marinol low dose | ACTIVE_COMPARATOR | - |
| Marinol high dose | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Nabiximols | DRUG | oromucosal spray |
| Placebo | DRUG | oromucosal spray |
| Sativex | DRUG | Oromucosal spray containing THC (27 mg/mL):CBD (25 mg/mL), in ethanol: propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each 100 μL spray delivered THC 2.7 mg and CBD 2.5 mg. The maximum number of daily sprays was 12. |
| Placebo (GA-0034) | DRUG | - |
| Sativex® | DRUG | containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum dose within any 24-hour interval is 12 sprays (THC 32.4 mg: CBD 30 mg) |
| GW-1000-02 | DRUG | Contained delta-9-tetrahydrocannabinol (THC) (27 mg/ml):cannabidiol (CBD) (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period. |
| GW-2000-02 | DRUG | Containing THC, 27 mg/ml, as extract of Cannabis sativa L. Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three hour period and 48 actuations (THC 130 mg) in 24 hours. |
| THC Alone | DRUG | Containing THC, 27 mg/ml, as extract of Cannabis sativa L. Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three hour period and 48 actuations (THC 130 mg) in 24 hours. |
| Temozolomide | DRUG | Oral capsule |
| Nabiximols-matched placebo | DRUG | Nabiximols-matched placebo oromucosal spray |
| Sativex Low Dose | DRUG | Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD. |
| Sativex Medium Dose | DRUG | Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD. |
| Sativex High Dose | DRUG | Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD. |
| Marinol | DRUG | Marinol dose level 1: 20 mg THC (2 marinol capsules) + 2 placebo capsules + 16 placebo sprays |
Inclusion Criteria: Screening (Visit 1) * Has had a diagnosis with any disease subtype of multiple sclerosis (MS), by revised 2017 McDonald criteria, for at least 12 months prior to Visit 1 and is expected to remain stable for the duration of the trial * Has a Modified Ashworth Scale (MAS) untrans...
Sativex is an investigational small molecule drug developed by Jazz Pharmaceuticals plc. It has been studied across several conditions, including multiple sclerosis, cerebral palsy, cancer, detrusor overactivity, hepatic impairment, and abuse potential evaluation. It is given in combination with other treatments in some studies, such as dose-intense temozolomide in recurrent glioblastoma.
Sativex has been studied for the treatment of spasticity in multiple sclerosis and in children with cerebral palsy. A Phase 3 trial, NCT01898520, evaluated its safety, efficacy, and tolerability for spasticity in patients aged 8 to 18 years with cerebral palsy. The multiple sclerosis indication is part of its clinical development program.
Sativex is developed by Jazz Pharmaceuticals plc, which trades under the ticker JAZZ. The company sponsors the clinical trials evaluating Sativex across its various indications, including cancer, cerebral palsy, and multiple sclerosis.
Sativex is in Phase 1 clinical development according to its overall program status. Individual trials have spanned Phase 1 and Phase 3, with six completed trials in total. It is an investigational drug and has not been approved by the FDA for the indications studied.
Sativex has been evaluated in six completed clinical trials, including NCT01898520 for spasticity in cerebral palsy, NCT01887301 in hepatic impairment, and NCT01812616 and NCT01812603 in recurrent glioblastoma. These trials enrolled a total of 1,110 participants and were randomized, double-blind, and placebo-controlled.