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Drug Trials Snapshots: OLINVYK

 

 

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the OLINVYK Package Insert for complete information.

OLINVYK (oliceridine)
Oh-LIN-vick
Trevena, Inc.
Approval date: August 7, 2020


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

OLINVYK is a drug for the treatment of acute pain in adults when the pain is severe enough to require an intravenous opioid.

How is this drug used?

OLINVYK is an injection. It is administered by a healthcare provider directly into the vein up to 27 milligrams per day.

What are the benefits of this drug?

OLINVYK reduces post-surgical pain. It is not available for home use.

What are the benefits of this drug (results of trials used to assess efficacy)?

The tables below summarize efficacy results for the evaluated patients for Trials 1 and 2. The efficacy was measured using the Summed Pain Intensity Differences (SPID) over 48 hours (SPID-48) or 24 hours (SPID-24), respectively. The SPID is calculated by multiplying the Pain Intensity,

Difference (calculated by subtracting the pain intensity at a particular timepoint from the pain intensity at baseline) scores at each post-baseline timepoint by the duration (in hours) since the preceding timepoint, and then summing the values, over 48 or 24 hours.

Table 1. SPID-48 Efficacy Endpoint Results in Trial 1

Efficacy Measure

 

OLINVYK

 

Placebo
regimen
(N=79)

0.35 mg regimen
(N=79)

0.5 mg regimen
(N=79)

Morphine
regimen
(N=76)

SPID-48

 

 

 

 

     Average

85 

138

164

193

     Differencea

---

47.5*  

80*

105*

     95 % Confidence Interval

 

(19, 75)

(52, 108)

(77, 132)

a. Treatment compared to placebo

Table 2. SPID-24 Efficacy Endpoint Results in Trial 2

 Efficacy Measure

OLINVYK

 

 

Placebo
regimen
(N=81)

0.35 mg regimen
(N=80)

0.5 mg regimen
(N=80)

Morphine
regimen
(N=83)

 

SPID-24

 

 

 

 

 

     Average

75

90

94

103

 

     Differencea

---

14*

18*

30*

 

     95 % Confidence Interval

 

(2, 26)

(5, 30)

(17, 42)

a. Treatment compared to placebo

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: OLINVYK worked similarly in men and women.
  • Race: OLINVYK worked similarly in White and Black or African American patients. The number of patients of other races was limited; therefore, differences in response for other races could not be determined.
  • Age: The number of patients 65 years of age or older was limited; therefore, differences in response between patients younger and older than 65 years could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below summarize efficacy results by subgroups for individual trials.

Table 3. Subgroup Analysis: SPID-48 Efficacy Results from Trial 1

Group

Subgroup

OLINVYK Difference from Placebo  (95% CI)a

0.35 mg regimen

0.5 mg regimen

 

Sex

Women

48.5   
(19.1, 77.8)

83.9   
(54.4, 113.4)

 

 

Men

45.8   
(-12, 103.6)

65.5   
(2.8, 128.1)

 

Raceb

Black or African American

37.6   
(-10.1, 85.3)

80.3   
(31, 129.7)

 

 

White

51.8   
(19.9, 83.8)

79.4   
(48.2, 110.5)

 

Ageb

≥ 18 to < 65 years

45.9   
(17.6, 74.2)

82.7   
(54.2, 111.2)

 

a Treatment differences and credible intervals include the relevance of outcomes from other subgroups.
b Results for patients 65 years or older and for other racial groups are not included due to the low number of enrolled patients in these groups.

Table 4. Subgroup Analysis: SPID-24 Efficacy Results from Trial 2

Group

Subgroup

OLINVYK Difference from Placebo (95% CI)a

 

0.35 mg regimen

0.5 mg regimen

Sexb

Women

14   
(1.6, 26.4)

18.1   
(5.5, 30.6)

Raceb

Black or African American

17.1   
(-2.8, 37)

20.2   
(1, 39.5)

 

White

12.2   
(-2.4, 26.9)

16.1   
(0.9, 31.2)

Ageb

≥ 18 to < 65 years

13.8   
(1.5, 26.2)

18.9   
(6.4, 31.5)

a Treatment differences and credible intervals include the relevance of outcomes from other subgroups.
b No males were included in either OLINVYK treatment group. c Results for men, patients 65 years or older and other racial groups are not included due to the low number of enrolled patients in these groups

FDA Statistical Review

What are the possible side effects?

OLINVYK may cause serious side effects including:

  • addiction and medication abuse,
  • life threatening breathing suppression,
  • life threatening withdrawal syndrome in a newborn whose mother received OLINVYK during pregnancy,
  • breathing problems, deep sedation, coma and death when used with other drugs that suppress brain function (such as benzodiazepines), and
  • severe drop in blood pressure.

The most common side effects are trials were nausea, vomiting, dizziness, headache, constipation, itchy skin and low oxygen levels in blood.

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions in patients with moderate to severe pain from each trial.

Table 5. Adverse Drug Reactions Reported in ≥5% of OLINVYK -Treated Patients Following Orthopedic Surgery-Bunionectomy (Trial 1)

Adverse Drug Reaction

Placebo

OLINVYK
0.35 mga

OLINVYK
0.5 mga

Morphineb

(N = 79)
%

(N = 79)
%

(N = 79)
%

(N = 76)
%

Any TEAEc (%)

68

86

91

96

Nausea

24

56

63

65

Vomiting

6

39

41

50

Dizziness

10

32

35

34

Somnolence

6

19

13

13

Constipation

11

11

14

17

Pruritus

8

15

4

20

Hypoxia

0

5

9

9

Sedation

1

5

4

3

Oxygen Saturation Decreased

0

4

5

9

 

Table 6. Adverse Drug Reactions Reported in ≥5% of OLINVYK -Treated Patients Following Plastic Surgery-Abdominoplasty (Trial 2)

Adverse Drug Reaction

Placebo

OLINVYK
0.35 mga

OLINVYK
0.5 mga

Morphineb

(N = 79)
%

(N = 79)
%

(N = 79)
%

(N = 76)
%

Any TEAEC (%)

78

94

95

98

Nausea

46

62

75

74

Vomiting

13

22

43

54

Hypoxia

5

20

18

23

Constipation

7

17

11

11

Pruritus

5

17

11

18

Dizziness

11

9

9

16

Sedation

8

14

9

23

Back pain

6

13

11

9

Somnolence

1

0

5

7

a Each OLINVYK regimen included a loading dose of 1.5 mg, followed by access to demand doses of 0.35 or 0.5 mg, with a 6-minute lockout period between doses, and 0.75-mg supplemental doses, beginning 1 hour after the initial dose, and hourly thereafter, as needed
 b The morphine regimen included a loading dose of 4 mg, followed by access to a demand dose of 1 mg, with a 6-minute lockout period between doses, and 2-mg supplemental doses, beginning 1 hour after the initial dose, and hourly thereafter, as needed. c Treatment Emergent Adverse Event

Table 7. Adverse Drug Reactions Reported in ≥5% of OLINVYK -Treated Patients in Trial 3

 Adverse Drug Reaction

 OLINVYK 
≤ 27mg 
N = 592

 OLINVYK
> 27mg
 N = 176

Patients with any TEAEa (%)

62

69

Nausea

29

38

Constipation

10

13

Vomiting

9

15

Headache

4

5

Hypokalaemia

4

7

Pruritus

4

8

Pyrexia

3

5

OLINVYK Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The overall occurrence of side effects was similar in men and women.
  • Race: The overall occurrence of side effects was similar in White and Black or African American patients. The number of patients of other races was limited; therefore, differences in response for other races could not be determined.
  • Age: The occurrence of side effects was similar across all tested age groups; however, the number of patients older than 65 years was limited

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The tables below summarize the occurrence of the adverse events by subgroup in pooled controlled trials (Trials 1 and 2).

Table 8. Adverse Events by Sex

 

          Placebo            
            N=162

       OLINVYK
           N=470

 Morphine    
       N=158

Women

Men

Women

       Men

Women

Men

N (%)

153 (94)

9 (6)

430 (91)

      40 (8)

145 (92)

13 (8)

% Patients with at least 1 AE

 

    75

 

 44

 

     90

 

         67

 

     97

 

  92

 

Percent Experiencing Selected AEs

Preferred Term

Women

Men

Women

Men

Women

Men

Nausea

37

11

59

32

72

46

Vomiting

10

0

32

15

53

38

Headache

31

11

26

17

30

31

 

Table 9. Adverse Events by Race

 

       Placebo     
              N=162

OLINVYK
      N=470

Morphine N=158

White

AA

White

AA

White

      AA

N (%)

 110 (68)

     48 (30)

310 (66)

130 (27)

104 (66)

   44 (28)

% Patients with at least 1 AE

   75

69

      89

     86

   98

     93

 

Percent Experiencing Selected AEs

Preferred Term

White

AA

White

AA

White

AA

Nausea

37

31

61

44

73

60

Vomiting

10

10

34

20

49

58

Headache

29

29

27

22

35

22

AA-Black or African American

 

Table 10. Adverse Events by Age

 

 

≥18-<50 years

≥50-<65 years

≥65-<70 years

≥70 years

  PI

    OL

   Mo

   PI

OL

Mo

PI

OL

Mo

PI

OL

Mo

N (%)

112
(69)

313
(67)

114
(72)

45
(2)

134
(28)

36
(23)

5
(3)

14
(3)

8
(5)

0

9
(2)

0

% Patients with at least 1 AE

 

72

 

89

 

97

 

82

 

87

 

94

 

20

 

93

 

100

 

0

 

67

 

0

 

Percent Experiencing Selected AEs

≥18-<50 years

≥50-<65 years

≥65-<70 years

≥70 years

Preferred Term

Pl

OL

Mo

Pl

OL

Mo

Pl

OL

Mo

Pl

OL

Mo

Nausea

38

57

76

31

55

56

0

57

37

0

33

0

Vomiting

10

32

53

11

29

44

0

36

62

0

22

0

Headache

26

23

25

42

31

39

0

43

50

0

11

0

Pl=placebo,
OL=OLINVYK,
Mo=morphine

Adapted from FDA Review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved OLINVYK based on evidence from three clinical trials (Trial 1/NCT02815709, Trial 2/NCT02820324 and Trial 3) of 1558 patients 18 to 89 years old who were in need for pain medication. The trials were conducted at 53 sites in the United States.

Patients from all three trials provided data for OLINVYK side effects and that population (safety population) is presented in the figures below. Separate trial populations are presented in Table 11 under MORE INFO.

Figure 1 summarizes the percentage of patients by sex in the combined clinical trials.

Figure 1. Demographics by Sex (safety population)

Pie chart summarizing how many men and women were in the clinical trial. In total, 1226  women (79%) and 332 men (21%) participated in the clinical trial

FDA Review

 

Figure 2 summarizes the percentage of patients by race in the in the combined clinical trials.

Figure 2. Demographics by Race (safety population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 1123 White (72%), 356 Black or African American  (23%), 36 Asian (2%), 10 American Indian and Alaska Native (1%) and 25 Other (2%)).

FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trials.

Figure 3. Demographics by Age (safety population)

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total,  1275 (82%) were less than 65 and 283 patients were 65 years and older (18%).)

FDA Review

Figure 4 summarizes the percentage of patients by ethnicity in the clinical trials.

Figure 4. Demographics by Ethnicity (safety population)

Pie charts summarizing ethnicity of patients enrolled in the clinical trial. In total, 289 patients were Hispanic or Latino (19%) and 1266 patients were not Hispanic or Latino (81%).

FDA Review

Who participated in the trials?

The table below summarizes demographics of all patients from the clinical trials.

Table 11. Demographic Characteristics for Trials 1, 2 and 3

Demographic Characteristics

Trial 1
N=389

Trial 2
N=401

Trial 3
N=768

Total
N=1558

Sex

 

 

 

 

  Men

59 (15.2)

3 (0.7)

270 (35.2)

332 (21.3)

  Women

330 (84.8)

398 (99.3)

498 (64.8)

1226 (78.7)

Race

 

  White

270 (69.4)

257 (64.1)

596 (77.6)

1123 (72.1)

  Black or African American

94 (24.2)

125 (31.2)

137 (17.8)

356 (22.8)

  Asian

14 (3.6)

9 (2.2)

13 (1.7)

36 (2.3)

  American Indian or Alaska Native

4 (1)

1 (0.2)

5(0.7)

10 (0.6)

  Native Hawaiian or Other Pacific Islander

4 (1)

3 (0.7)

1 (0.1)

8 (0.5)

  Other

3 (0.8)

6 (1.5)

14 (1.8)

23 (1.5)

   Missing

0

0

2 (0.3)

2 (0.1)

Age (years)

 

 

 

 

  Median (min, max)

47 (19, 74)

41 (20, 71)

53 (18,89)

48 (18,89)

Age Group

 

  18 to <50 years

220 (56.6)

319 (79.6)

286 (37.2)

825 (52.9)

  50 to <65 years

143 (36.8)

72 (17.9)

235 (30.6)

450 (28.9)

  65 to <70 years

18 (4.6)

9 (2.2)

109 (14.2)

136 (8.7)

  ≥ 70 years

8 (2)

1 (0.2)

138 (17.9)

147 (9.4)

Ethnicity

 

   Hispanic or Latino
 

96 (24.7)

132 (32.9)

61 (7.9)

289 (18.5)

   Not Hispanic or Latino

293 (75.3)

269 (67.1)

704 (91.7)

1266 (81.3)

    Missing

0

0

3 (0.4)

3 (0.2)

Region

 

  United States

389 (100)

401 (100)

768 (100)

1558 (100)

Clinical Trial Data

How were the trials designed?

Trials 1 enrolled patients who underwent bunion surgery. Patients with moderate to severe post-surgical pain were randomly assigned to receive OLINVYK, placebo or an approved drug to treat pain (morphine) for 48 hours through the vein. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. All patients were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.

Trial 2 enrolled patients who underwent surgical removal of abdominal wall fat (abdominoplasty) and had moderate to severe pain. Patients were randomly assigned to receive OLINVYK, placebo or an approved drug to treat pain (morphine) for 24 hours through the vein. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. All patients were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.

To assess the benefits of OLINVYK, patients used a numerical scale to score how severe the pain was after the surgery. The scores for the patients receiving OLINVYK were compared to the scores for the patients who received placebo and those who received morphine.

In the third trial, patients who had pain following various type of surgeries or due to a medical condition received at least one dose of OLINVYK. Data from this trial were used only to assess the side effects of OLINVYK.

How were the trials designed?

The efficacy and safety of OLINVYK were established in two randomized, double-blind, placebo-and active (morphine) -controlled trials. Trials 1 and 2 evaluated OLINVYK for the treatment of moderate to severe post-operative pain. Patients in Trial 1 had undergone a bunionectomy and received either placebo, morphine, OLINVYK 0.1 mg, OLINVYK 0.35 mg, or OLINVYK 0.5 mg for 48 hours. Patients in Trial 2 had undergone abdominoplasty and received either placebo, morphine, OLINVYK 0.1 mg, OLINVYK 0.35 mg, or OLINVYK 0.5 mg for 24 hours. If trial medication was inadequate, patients may have received rescue pain medication.

The analgesic effect was measured using the Summed Pain Intensity Differences over 48 hours (SPID-48) or 24 hours (SPID-24), respectively. The SPID is calculated by multiplying the Pain Intensity Difference (calculated by subtracting the pain intensity at a particular timepoint from the pain intensity at baseline) scores at each post-baseline timepoint by the duration (in hours) since the preceding timepoint, and then summing the values, over 48 or 24 hours.

Trial 3 was an open-label safety evaluation of OLINVYK at various doses in medical and surgical patients.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

LINK TO PRESCRIBING INFORMATION

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